Paraneoplastic seesaw nystagmus and opsoclonus provides evidence for hyperexcitable reciprocally innervating mesencephalic network

J Neurol Sci. 2018 Jul 15:390:239-245. doi: 10.1016/j.jns.2018.05.002. Epub 2018 May 3.


Seesaw nystagmus is characterized by the rhythmic combination of vertical and torsional dysconjugate oscillations where one eye moves up and inward while the other moves down and outward. Common association of seesaw nystagmus with accessory optic track lesions lead to traditional hypothesis that it is due to the mismatch in the vision and vestibular systems. Here we propose a novel mechanism for seesaw nystagmus. We hypothesize that reverberations due to abnormal increases in the excitability of the reciprocally innervating circuit of excitatory burst neuron in the midbrain interstitial nucleus of Cajal causes the seesaw nystagmus. Analogous oscillations of the brainstem burst generators may be responsible for generation of saccadic oscillations or opsoclonus. The key difference is that the interstitial nucleus of Cajal lacks inhibitory burst neurons, hence the lack of post-inhibitory rebound, and relatively lower frequency of the oscillatory cycles causing pendular seesaw nystagmus. In contrast the brainstem burst generator, with reciprocally innervating excitatory and inhibitory burst neurons, and further inhibitory influence of the omnipause neurons results in the post-inhibitory rebound at the burst neurons, hence high oscillation frequency. This novel concept is supported by a unique observation in a patient with antineuronal nuclear autoantibody type 2 due to breast cancer who had combined seesaw nystagmus and superimposed saccadic oscillations. The patient neither had cerebellar deficits typically thought to cause paraneoplastic opsoclonus nor visual deficits that are known cause of seesaw nystagmus. We propose that hyperexcitability of the burst neurons in the interstitial nucleus of Cajal due to paraneoplastic antibody caused pendular seesaw nystagmus. On the other hand, increased excitability of brainstem burst generators and reduced efficacy of the omnipause neurons caused saccadic oscillations.

Keywords: Cerebellum; Interstitial nucleus of Cajal; Pendular nystagmus; Post-inhibitory rebound.

Publication types

  • Case Reports
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Antinuclear
  • Antibodies, Neoplasm / immunology
  • Breast Neoplasms / complications
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / physiopathology
  • Carcinoma, Small Cell / complications
  • Carcinoma, Small Cell / drug therapy
  • Carcinoma, Small Cell / physiopathology
  • Computer Simulation
  • Female
  • Humans
  • Mesencephalon / physiopathology*
  • Middle Aged
  • Models, Neurological*
  • Neural Inhibition / physiology
  • Neural Pathways / physiopathology
  • Neurons / physiology
  • Nystagmus, Pathologic / complications
  • Nystagmus, Pathologic / physiopathology*
  • Nystagmus, Pathologic / therapy
  • Ocular Motility Disorders / complications
  • Ocular Motility Disorders / physiopathology*
  • Ocular Motility Disorders / therapy
  • Paraneoplastic Syndromes / complications
  • Paraneoplastic Syndromes / physiopathology*
  • Paraneoplastic Syndromes / therapy
  • Periodicity


  • ANNA-2 antibody, human
  • Antibodies, Antinuclear
  • Antibodies, Neoplasm