title: The Equine Movement Disorder "Shivers" Is Associated With Selective Cerebellar Purkinje Cell Axonal Degeneration.
abstract: "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.
authors.affiliation: Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St Paul, MN, USA valbe001@umn.edu.
authors.forename: S J
authors.initials: SJ
authors.lastname: Valberg
authors.affiliation: Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St Paul, MN, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Lewis
authors.affiliation: Veterinary Diagnostic Laboratory, University of Minnesota, St Paul, MN, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Shivers
authors.affiliation: Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St Paul, MN, USA.
authors.forename: N E
authors.initials: NE
authors.lastname: Barnes
authors.affiliation: School of Kinesiology, University of Minnesota, Minneapolis, MN USA.
authors.forename: J
authors.initials: J
authors.lastname: Konczak
authors.affiliation: Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St Paul, MN, USA.
authors.forename: A C E
authors.initials: AC
authors.lastname: Draper
authors.affiliation: Department of Veterinary Population Medicine, College of Veterinary Medicine, University of Minnesota, St Paul, MN, USA Veterinary Diagnostic Laboratory, University of Minnesota, St Paul, MN, USA.
authors.forename: A G
authors.initials: AG
authors.lastname: Armién
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology; D064032:Calbindin 2 / Q000378:metabolism; D002490:Central Nervous System / Q000473:pathology; D006734:Horse Diseases / Q000473:pathology*; D006736:Horses; D008297:Male; D009069:Movement Disorders / Q000473:pathology / Q000662:veterinary*; D009186:Myelin Sheath / Q000473:pathology; D009207:Myoclonus / Q000473:pathology / Q000662:veterinary*; D009410:Nerve Degeneration / Q000473:pathology / Q000662:veterinary*; D000069338:Neuropathology; D010525:Peripheral Nerves / Q000473:pathology; D011689:Purkinje Cells / Q000473:pathology
chemical_list: D064032:Calbindin 2
keywords: Purkinje cell; axonal degeneration; cerebellum; horse; myelin decompaction; myoclonus; shivering