Progressive limb ataxia following inferior olive lesions


A. R. Gibson: Division of Neurobiology, Barrow Neurological Institute, 350 West Thomas Road, Phoenix, AZ 85013, USA. Email:

Key points

  • • The inferior olive (IO) provides climbing fibre input to the cerebellum. Kainic acid lesions of rostral IO of the cat produce several distinct movement deficits.
  • • Vestibular disturbances are apparent the first few days after injection but rapidly recover.
  • • Disturbances of grasping occur immediately and do not recover over months of testing.
  • • After a brief delay, limb movements during reaching and locomotion show a progressive development of ataxia that becomes severe over months of testing.
  • • The decomposition of movement during reaching and alterations in reach trajectories are similar to those seen in humans with cerebellar ataxias – degeneration of the IO may contribute to the progressive nature of these diseases.

Abstract  Cerebellar climbing fibres originate in the inferior olive (IO). Temporary IO inactivation produces movement deficits. Does permanent inactivation produce similar deficits and, if so, do they recover? The excitotoxin, kainic acid, was injected into the rostral IO of three cats. Behaviour was measured during reaching and locomotion. Two cats were injected during the reaching task. Within minutes, grasping became difficult and the trajectories of the reaches showed higher arcing than normally seen. During locomotion, both cats showed head and trunk deviation to the injected side, walking paths curved to the injected side, and the paws were lifted higher than normal. Limbs contralateral to the injections became rigid. Within 1 day, posture had normalized, locomotion was unsteady and high lifting of the paws had reversed to a tendency to drag the dorsum of the paws. Passive body movement produced vestibular signs. Over a few days, locomotion normalized and vestibular signs disappeared. Reach trajectories were normal but grasping deficits persisted. Over the first week, the amplitude of limb lift during reaching and locomotion began to increase. The increase continued over time and, after several months, limb movements became severely ataxic. The effects followed the somatotopy of the rostral IO: a loss of cells in medial rostral IO only affected the forelimb, whereas a loss of cells in medial and lateral IO affected both forelimb and hindlimb. Deficits produced by IO lesions involve multiple mechanisms; some recover rapidly, some appear stable, and some worsen over time. The nature of the progressive deficit suggests a gradual loss of Purkinje cell inhibition on cerebellar nuclear cells.