Ocular-Motor Profile and Effects of Memantine in a Familial Form of Adult Cerebellar Ataxia with Slow Saccades and Square Wave Saccadic Intrusions

Abstract

Fixation instability due to saccadic intrusions is a feature of autosomal recessive spinocerebellar ataxias, and includes square wave intrusions (SWI) and macrosaccadic oscillations (MSO). A recent report suggested that the non-competitive antagonist of NMDA receptors, memantine, could decrease MSO and improve fixation in patients with spinocerebellar ataxia with saccadic intrusions (SCASI). We similarly tested two sisters, respectively of 58 and 60 years, with an unrecognized form of recessive, adult-onset cerebellar ataxia, peripheral neuropathy and slow saccades, who showed prominent SWI and also complained with difficulty in reading. We tested horizontal visually guided saccades (10°–18°) and three minutes of steady fixation in each patient and in thirty healthy controls. Both patients showed a significant reduction of peak and mean velocity compared with control subjects. Large SWI interrupting steady fixation were prominent during steady fixation and especially following visually guided saccades. Eye movements were recorded before and during the treatment with memantine, 20 mg/daily for 6 months. The treatment with memantine reduced both the magnitude and frequency of SWI (the former significantly), but did not modified neurological conditions or saccade parameters. Thus, our report suggests that memantine may have some general suppressive effect on saccadic intrusions, including both SWI and MSO, thereby restoring the capacity of reading and visual attention in these and in other recessive forms of ataxia, including Friedreich’s, in which saccadic intrusions are prominent.

A simple saccadic reading test to assess ocular motor function in cerebellar ataxia

“…Infrared oculography during regularly spaced single-digit number reading showed that slower reading in ataxia patients was due to abnormal saccade and fixation behavior, which are well reported with eye movement recording studies of reflexive eye movement and fixation in cerebellar ataxia [ 12 , 29 , 31 , 55 , 56 ]. These abnormalities lead to more frequent and abnormal saccades and fixations during reading [ 31 , 34 , 36 ] as well as other visual tasks [ 57 ].…”

Altered Actions of Memantine and NMDA-Induced Currents in a New Grid2-Deleted Mouse Line

“…Gait disorders are a common pathology in patients with spinocerebellar degeneration, and are sometimes accompanied by vertigo resulting from oculomotor dysfunction [ 25 , 26 ]. Memantine also affects oculomotor functions in patients with cerebellar ataxia [ 27 ]. To examine whether our mutant mice also had oculomotor impairments, we measured the OKR and OKR adaptation, a form of cerebellum-dependent learning [ 28 , 29 ], and used the results from these assays to quantify memantine susceptibility ( Supplementary Figure S1 ).…”

Characteristic Eye Movements in Ataxia-Telangiectasia-Like Disorder: An Explanatory Hypothesis

“…Eye movements were measured using a video-based, remote, monocular recording, two-dimensional eye tracking technique (ASL 504, sample rate: 240 Hz) ( 15 ). The experiment was designed to study horizontal visually guided saccades (10°–18°) ( 16 ) and steady fixation in primary and eccentric positions (10°–18°), in order to study SI and nystagmus ( 17 ). Due to the head and neck dystonia which induced unbearable fatigue and poor compliance during the head constraint, patients performed a series of independent experiments on different sessions (in a period lasting 1 year).…”

“…MSO were back to back hypermetric saccades, with an intersaccadic interval of about 200 ms; they oscillated around the target and spontaneously grew larger and then smaller (in amplitude). The quantitative characterization of SI included amplitude of saccades, their intersaccadic interval, and frequency of square-wave SI ( 17 ) or frequency of oscillations in MSO. Nystagmus was characterized by alternation of slow drift of the eye position (slow phase) followed by a rapid correction (quick phase).…”