Effects of 4-aminopyridine on nystagmus and vestibulo-ocular reflex in ataxia-telangiectasia

Aasef G. Shaikh, Sarah Marti, Alexander A. Tarnutzer, Antonella Palla, Thomas O. Crawford, David S. Zee, Dominik Straumann

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)2728-2735
Number of pages8
JournalJournal of neurology
Volume260
Issue number11
DOIs
StatePublished - Nov 2013

Keywords

  • Cerebellum
  • Eye movements
  • GABA
  • Gaze holding
  • Integrator

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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