Opsoclonus in three dimensions: oculographic, neuropathologic and modelling correlates

Opsoclonus is a dyskinesia consisting of involuntary, arrhythmic, chaotic, multidirectional saccades, without intersaccadic intervals. We used a magne tic scleral search coil technique to study opsoclonus in two patients with paraneoplastic complications of lung carcinoma. Eye movement recordings pro vided evidence that opsoclonus is a three-dimensional oscillation, consisti ng of torsional, horizontal, and vertical components. Torsional nystagmus w as also present in one patient. Antineuronal antibody study revealed the pr esence of anti-Ta (Ma2 onco-neuronal antigen) antibodies in one patient, wh ich had previously been associated only with paraneoplastic limbic encephal itis and brainstem dysfunction, but not opsoclonus, and only in patients wi th testicular or breast cancer. Neuropathologic examination revealed mild p araneoplastic encephalitis. Normal neurons identified in the nucleus raphe interpositus (rip) do not support postulated dysfunction of omnipause cells in the pathogenesis of opsoclonus. Computer simulation of a model of the s accadic system indicated that disinhibition of the oculomotor region of the fastigial nucleus (FOR) in the cerebellum can generate opsoclonus. Histopa thological examination revealed inflammation and gliosis in the fastigial n ucleus. This morphological finding is consistent with, but not necessary to confirm, damage to afferent projections to the FOR, as determined by the m odel. Malfunction of Purkinje cells in the dorsal vermis, which inhibit the FOR, tray cause opsoclonus by disinhibiting it. (C) 2001 Elsevier Science B.V. All rights reserved.