Physiological and pathological aspects of Saccades: new approaches to diagnosis and treatment of saccadic abnormalities

Introduction: Eye movements represent a scientific tool that can be reliably used for characterizing both physiological and pathological aspects concerning the central nervous system. This thesis focuses on the study of horizontal saccades conjugacy using a novel approach, such as the phase-plane technique, and the treatment of a specific eye movement disorder, such as saccadic intrusions, with memantine. Methods: We recorded horizontal saccades in 22 patients with disease affecting different sites from the brainstem to the extraocular muscles, and used the phase-plane technique to plot the velocity difference between the two eyes. Two patients affected by spinocerebellar ataxia with saccadic intrusions (SCASI) were treated with memantine. Results: Patients with disorders of the brainstem or the cranial nerves show abnormal velocity disconjugacy in the first 10% of eye displacement, while patients with myasthenia gravis may do so later in the course of the saccade. Patients with disease affecting the extraocular muscles show only minor initial disconjugacy. After treatment with memantine, the frequency of saccadic intrusions was reduced of about 50% in both patients. Conclusions: Preservation of conjugacy of the initial saccadic movement on binocular phase planes in myasthenia and chronic progressive external ophthalmoplegia, suggests that the pale global fibers of the extraocular muscles drive the initial, high-acceleration component of saccades. Saccadic intrusions in SCASI patients may occur when excitatory inputs from mossy fiber collaterals to deep cerebellar nuclei are not suppressed by inhibition from cerebellar cortex. Memantine may reduce the excitatory effect of mossy fiber collaterals on cerebellar deep nuclei, thereby reducing the probability of an unwanted saccade.