title: Effects of 4-aminopyridine on nystagmus and vestibulo-ocular reflex in ataxia-telangiectasia.
abstract: Ataxia-telangiectasia (A-T) is a progressive neurodegenerative disorder with prominent eye movement deficits localizing to the cerebellum. We sought to determine if 4-aminopyridine (4-AP), which putatively enhances the precision of Purkinje neurons, could improve the disorders of eye movements and vestibular function in A-T. The influence of 4-AP on disorders of eye movements and vestibular function was studied in four A-T patients. The effects on the cerebellar control of vestibulo-ocular reflex (VOR) was quantitatively assessed by the decay time constant of per- and post-rotational nystagmus during constant velocity en bloc rotations. The length of the VOR time constant determines the fidelity of the vestibular velocity storage, a neural mechanism that increases the bandwidth of VOR under cerebellar control. The VOR time constant was not increased in A-T patients. The latter is explained by the extent of cerebellar lesion as previously described in A-T and other cerebellar disorders. Nevertheless, 4-AP shortened the VOR time constant during horizontal rotations. Severe disinhibition of velocity storage in subjects with putatively profound cerebellar degeneration manifest periodic alternating nystagmus (PAN). Among two A-T subjects who manifested PAN, 4-AP reduced the peak slow phase velocity of the more severely affected individual and abrogated the PAN in the other. Two A-T subjects manifested horizontal and vertical spontaneous nystagmus (SN) in primary gaze, 4-AP reduced its slow phase velocity. We conclude that in subjects with A-T 4-AP has a prominent effect on the ocular motor and vestibular deficits that are ascribed to the loss of cerebellar Purkinje neurons.
authors.affiliation: Department of Neurology, Emory University School of Medicine, Wesley Woods Health Center, 1841 Clifton Road, NE, Suite 350, Atlanta, GA, 30329-4021, USA, aasefshaikh@gmail.com.
authors.forename: Aasef G
authors.initials: AG
authors.lastname: Shaikh
authors.forename: Sarah
authors.initials: S
authors.lastname: Marti
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Tarnutzer
authors.forename: Antonella
authors.initials: A
authors.lastname: Palla
authors.forename: Thomas O
authors.initials: TO
authors.lastname: Crawford
authors.forename: David S
authors.initials: DS
authors.lastname: Zee
authors.forename: Dominik
authors.initials: D
authors.lastname: Straumann
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology / Q000627:therapeutic use*; D000328:Adult; D001260:Ataxia Telangiectasia / Q000150:complications* / Q000188:drug therapy; D006801:Humans; D008875:Middle Aged; D009759:Nystagmus, Pathologic / Q000188:drug therapy* / Q000209:etiology*; D026902:Potassium Channel Blockers / Q000494:pharmacology / Q000627:therapeutic use*; D012027:Reflex, Vestibulo-Ocular / Q000187:drug effects; D012399:Rotation; D013997:Time Factors; D060726:Torso / Q000502:physiology; D015837:Vestibular Diseases / Q000188:drug therapy* / Q000209:etiology*
chemical_list: D026902:Potassium Channel Blockers; D015761:4-Aminopyridine