Eye movement disorders in MS are frequently misdiagnosed and frequently overlooked during clinical examination. Even at a subclinical state, these defects frequently cause disability and weariness [11].
Regarding eye movements impairment, abnormal saccades are very prevalent in MS, occurring in 30% Cipparrone et al. [12] patients, 36% of Degirmenci et al. [8] cases, and 65% of Kenig et al. [13] cases. Recording saccades permits the evaluation of subclinical ocular motor disorders. Using ENG, Grénman examined the three characteristics of saccadic movements (precision, velocity, and latency). In 36% of cases, prolonged latencies were observed [14]. However, this characteristic is affected by various variables, including age, brightness, simultaneous auditory stimulus, and visual acuity. Brainstem lesions are strongly associated with low saccade velocity. In fact, saccade velocity slowed to as low as 200°/s often. Dysmetria is associated with cerebellar lesions [15]. It was identified in 44% of patients in the Grenman series [16], 32% of cases in the Serra et al. [17] series, and 45% in our study.
Smooth pursuit anomalies are widespread (30 to 70%) in MS [8, 12, 14, 15, 18, 19]. An isolated gain deficiency in pursuit eye movements is uncommon, and it is frequently accompanied with abnormalities in saccades, particularly dysmetria [16]. In MS, abnormal OKN is commonly observed. Both brainstem and cerebellar lesions have been associated with a decreased velocity of the OKN slow phase. Eleven individuals in our series revealed abnormal OKN. The MRI of their brains indicated infratentorial lesions in 82% of instances. In addition, it was revealed that individuals with brainstem lesions had slower saccade velocities than those with cerebellar involvement [14, 20]. However, Cogan et al. [21] mention pathologic OKN as one of the ocular symptoms indicating cerebellar involvement. On the contrary, precision problems are more closely associated with cerebellar disorders [22].
Different lesions of the central nervous system, particularly infratentorial placement, are associated with tracking problems [23, 24]. More than half of the eleven patients with infratentorial lesions in our research showed abnormal tracking results.
MS patients may have peripheral or central vestibular abnormalities. Overall prevalence of real vertigo is less than 5% [25]. However, complaints regarding imbalance and other balance disorders are more frequent.
In MS, nystagmus is more prevalent during relapses. In his sample of 56 MS patients with balance difficulties during relapses, Cohen [26] reported nystagmus in 64% of cases; nearly half of them had central type nystagmus. In MS, acquired pendular nystagmus is present in 11 to 20% of the cases, often accompanied by internuclear ophthalmoplegia or optic neuropathy, and most frequently observed in the progressive form of the disease [13, 17, 27]. A total of 6.7% of MS patients present with central positional type nystagmus [28].
In MS, caloric testing reveals anomalies in H-VOR, vestibular reflectivity, and directional predominance. H-VOR abnormalities are really one of the most prevalent ocular motor abnormalities in MS. In 36% of MS sufferers, Downey et al. [29] identified VOR abnormalities. In half of the patients in our series, VOR gain abnormalities were found (10 patients). Seven patients (35%) had hyporeflectivity (VOR low gain), while three patients (15%) exhibited hyperreflectivity. A reduction in VOR gain is often associated with bilateral peripheral vestibular lesions or lesions of the brainstem [30]. In contrast, an unusually elevated VOR gain is uncommon and is typically linked with cerebellar lesions [31]. Caloric directional preponderance was seen in 28% of Aantaa et al [32].’s series, 48% of Grenman’s [33] series, and 50% of our series.
The underlying pathophysiology is related to the mechanism of stable gaze holding that requires a neural integrator that converts the pulses of neural firing into a constant firing rate.
The integrator relies on feedback, altered feedback behaves as an “unstable” integration if it is too strong, and as a “leaky” integration if it is too weak [34].
Horizontal eye movement neural integrator is located in the pons (paramedian pontine reticular formation) and upper part of the medulla (nucleus prepositus hypoglossi and medial vestibular nucleus). Feedback information is delivered from the cerebellum (fastigial nucleus, dorsal vermis, flocculus, and nodulus).
The medial vestibular nucleus is a key element for neural integration of horizontal eye movements. It receives feedback from various cerebellum and brainstem structures such as flocculus and nodulus [34]. Cerebellar feedback deficit manifests as neural integrator decreased gain and reveals its inherently imperfect behavior, resulting in a decelerating drift in eye position followed by a visually driven corrective saccade (quick phase of the jerk nystagmus) that refocuses the eye on the area of interest on target. Drift velocity increases as the eye moves away from the center [34,35,36,37].
In rare cases, the slow-phase velocity of the drift increases exponentially; this phenomenon, known as increased frequency or “runaway” nystagmus, can also be explained by an increase in feedback gain, resulting in instability of the neural integrator [34, 35].
Other factors can also explain jerky oscillations in subjects with multiple sclerosis such as vestibular alteration or hypofunction due to the demyelinating plaque affecting the vestibular nuclei which manifest as peripheral vestibular lesion [34].
