Saccadic oscillations after doping suggest a possible mechanism for cerebellar and omnipause neurons dysfunction (P5.311)

OBJECTIVE: To report on two cases of opsoclonus associated with doping and propose a hypothesis for the underlying pathological mechanism. BACKGROUND: Opsoclonus is a rare disorder consisting in involuntary, arrhythmic, conjugate saccadic oscillations without intersaccadic intervals. Cerebellar ataxia, postural tremor, and behavioral disturbances are often associated. Several etiologies have been identified; however the exact pathological mechanism remains still unclear. Disinhibition of cerebellar fastigial nuclei and/or reduction of glycinergic inhibition on the brainstem saccadic burst neurons have been hypothesized as possible causes. METHODS: Two male tennis players (32 and 34 yrs) developed rapidly progressive blurred vision and oscillopsia associated with ataxia, vertigo, tremor, and preceded by behavioral changes. Personal and familial history was collected. Both subjects received an accurate clinical and neurological evaluation including neuro-imaging, blood, and CSF examination. RESULTS: Opsoclonus was diagnosed in both patients. In one patient, eye movements recording revealed spindle-shaped oscillations, suggesting combined cerebellar dysmetria and impaired omnipause neurons activity. Common metabolic, neoplastic, infectious, auto-immune, and toxic causes of opsoclonus were excluded. Both subjects, however, reported a recent doping practice with illegally synthetized compounds. Anabolic androgenic steroids were isolated from one sample of the compound. CONCLUSIONS: Combined cerebellar and brainstem damage might be the trigger of opsoclonus. Anabolic androgenic steroids can alter neuronal activity by inducing allosteric modulation and abnormal expression of GABA receptors. GABA receptors are present on omnipause and cerebellar neurons. Although a clear dependency cannot be established in our cases, anabolic steroids might have contributed to the onset of opsoclonus by action on GABAergic receptors leading to inhibition of omnipause neurons, with consequent hyperexcitability of brainstem burst neurons, and to cerebellar dysfunction causing fastigial disinhibition. Study supported by: Intramural Research Program of NEI and FP7-PEOPLE-2010-IRSES CERVISO 269263 Disclosure: Dr. Pretegiani has nothing to disclose. Dr. Rosini has nothing to disclose. Dr. Rocchi has nothing to disclose. Dr. Ginanneschi has nothing to disclose. Dr. Optican has nothing to disclose. Dr. Rufa has nothing to disclose.