Nystagmus: Diagnosis, Topographic Anatomical Localization and Therapy

Nystagmus is defined as rhythmic, most often involuntary eye movements. It normally consists of a slow (pathological) drift of the eyes, followed by a fast central compensatory movement back to the primary position (refixation saccade). The direction, however, is reported according to the fast phase. The cardinal symptoms are, on the one hand, blurred vision, jumping images (oscillopsia), reduced visual acuity and, sometimes, double vision; many of these symptoms depend on the eye position. On the other hand, depending on the etiology, patients may suffer from the following symptoms: 1. permanent dizziness, postural imbalance, and gait disorder (typical of downbeat and upbeat nystagmus); 2. if the onset of symptoms is acute, the patient may experience spinning vertigo with a tendency to fall to one side (due to ischemia in the area of the brainstem or cerebellum with central fixation nystagmus or as acute unilateral vestibulopathy with spontaneous peripheral vestibular nystagmus); or 3. positional vertigo. There are two major categories: the first is spontaneous nystagmus, i.e., nystagmus which occurs in the primary position as upbeat or downbeat nystagmus; and the second includes various types of nystagmus which are induced or modified by certain factors. Examples are gaze-evoked nystagmus, head-shaking nystagmus, positional nystagmus, and hyperventilation-induced nystagmus. In addition, there are disorders similar to nystagmus, such as ocular flutter or opsoclonus. The most common central types of spontaneous nystagmus are downbeat and upbeat, infantile, pure torsional, pendular fixation, periodic alternating, and seesaw nystagmus. Many types of nystagmus allow a precise neuroanatomical localization: for instance, downbeat nystagmus, which is most often caused by a bilateral floccular lesion or dysfunction, or upbeat nystagmus, which is caused by a lesion in the midbrain or medulla. Examples of drug treatment are the use of 4-aminopyridine for downbeat and upbeat nystagmus, memantine or gabapentin for pendular fixation nystagmus, or baclofen for periodic alternating nystagmus. In this article we are focusing on nystagmus. In a second article we will focus on central ocular motor disorders, such as saccade or gaze palsy, internuclear ophthalmoplegia, and gaze-holding deficits. Therefore, these types of eye movements will not be described here in detail.

Effects of Acetyl-DL-Leucine on Ataxia and Downbeat-Nystagmus in Six Patients With Ataxia Telangiectasia

Background: There is no authorized treatment for ataxia telangiectasia (AT). As cerebellar symptoms of storage diseases were improved by acetyl-DL-leucine (ADLL), the authors hypothesized a symptomatic and disease-modifying effect in AT upon supplementation with ADLL. Methods: Six patients were treated with ADLL 3 g/day for 1 week followed by 5g/day for 3 weeks to 1 year. Cerebellar ataxia was evaluated by validated scales. Gaze-holding, saccades and smooth pursuit were examined by video-oculography. Measurements took place at baseline, at 1 month of therapy in 5 patients, and after 6 and 12 months in 1 patient. Results: The Scale for Assessment and Rating of Ataxia changed from the baseline, mean, (SD, min-max) of 22.1 (5.88, 11-28.5) to 18 points (5.39, 8.5-23.5) after 1 month on medication ( P = .0028). All patients demonstrated gaze-holding deficits; 3 patients had central-position downbeat-nystagmus. Mean slow-phase velocity of this nystagmus with the gaze straight-ahead changed from 5.57°/s (1.8, 3.53-6.99) to 4.7°/s (0.79, 3.97-5.56) after 1 month on treatment (1.35, -2.56-4.17) ( P = .046). Interpretation: ADLL may improve ataxia and ocular stability in AT patients, while the molecular basis still remains to be elucidated. A multicentric, rater-blinded, phase II trial currently investigates the effects of acetyl-L-leucine in AT (NCT03759678).

Stiff-Eye Syndrome—Anti-GAD Ataxia Presenting with Isolated Ophthalmoplegia: A Case Report

Anti-GAD ataxia is one of the most common forms of immune-mediated cerebellar ataxias. Many neurological syndromes have been reported in association with anti-GAD. Ophthalmoparesis has been described in stiff person syndrome. We report a case of anti-GAD ataxia presenting initially with isolated ophthalmoplegia and showing complete resolution after immunotherapy. A 26-year-old male patient presented with ophthalmoparesis characterized by tonic upwards deviation of the right eye. In the following month, he developed progressive ataxia with anti-GAD titers of 1972 UI/mL. After treatment with methylprednisolone and immunoglobulin, there was complete resolution of symptoms and anti-GAD titers decreased. This is the first report of isolated ophthalmoparesis due to tonic eye deviation associated with anti-GAD antibodies without stiff-person syndrome. Tonic eye deviation has been reported in SPS, possibly secondary to continuous discharge in gaze holding neurons in the brainstem (similar to what occurs in spinal motor neurons). With growing evidence for ocular abnormalitites in SPS, anti-GAD associated neurological syndromes should be included in the differential diagnosis of isolated ophthalmoplegia.

Fixation eye movement abnormalities and stereopsis recovery following strabismus repair

We evaluated the effects of strabismus repair on fixational eye movements (FEMs) and stereopsis recovery in patients with fusion maldevelopment nystagmus (FMN) and patients without nystagmus. Twenty-one patients with strabismus, twelve with FMN and nine without nystagmus, were tested before and after strabismus repair. Eye-movements were recorded during a gaze-holding task under monocular viewing conditions. Fast (fixational saccades and quick phases of nystagmus) and slow (inter-saccadic drifts and slow phases of nystagmus) FEMs and bivariate contour ellipse area (BCEA) were analyzed in the viewing and non-viewing eye. Strabismus repair improved the angle of strabismus in subjects with and without FMN, however patients without nystagmus were more likely to have improvement in stereoacuity. The fixational saccade amplitudes and intersaccadic drift velocities in both eyes decreased after strabismus repair in subjects without nystagmus. The slow phase velocities were higher in patients with FMN compared to inter-saccadic drifts in patients without nystagmus. There was no change in the BCEA after surgery in either group. In patients without nystagmus, the improvement of the binocular function (stereopsis), as well as decreased fixational saccade amplitude and intersaccadic drift velocity, could be due, at least partially, to central adaptive mechanisms rendered possible by surgical realignment of the eyes. The absence of improvement in patients with FMN post strabismus repair likely suggests the lack of such adaptive mechanisms in patients with early onset infantile strabismus. Assessment of fixation eye movement characteristics can be a useful tool to predict functional improvement post strabismus repair.

Acquired nystagmus

Nystagmus is the repetitive to and fro movement of the eyes, which may be physiological or pathological. The movements can be horizontal, vertical, torsional or a combination of these movements. It starts by a slow movement of the eye away from the visual target. The second movement brings the eye back to the visual target. If this second movement is quick, the nystagmus is called jerk nystagmus. If the second movement is slow, the nystagmus is said to be pendular. Maintaining steady gaze is dependent upon visual fixation, the vestibulo-ocular reflex and the gaze-holding neural integrator system. Pathological nystagmus typically presents with the symptom of oscillopsia, which is the illusory movement of the surrounding environment. Nystagmus that develops outside of early infancy is termed acquired nystagmus. There may be serious underlying pathology that will require further investigation and management. This article reviews the terminology, pathophysiology, causes and treatment of acquired nystagmus.

Cerebellar Dizziness and Vertigo: Etiologies, Diagnostic Assessment, and Treatment

Cerebellar dizziness and vertigo account for approximately 10% of diagnoses in a tertiary dizziness center. This term summarizes a large group of disorders with chronic (degenerative, hereditary, acquired cerebellar ataxias), recurrent (episodic ataxias), or acute (stroke, inflammation) presentations. Key to the diagnosis is a comprehensive examination of central ocular motor and vestibular function. Patients with cerebellar dizziness and vertigo usually show a pattern of deficits in smooth pursuit, gaze-holding, saccade accuracy, or fixation-suppression of the vestibulo-ocular reflex. Central fixation nystagmus (e.g., downbeat nystagmus), gaze-evoked nystagmus, central positional nystagmus, or head-shaking nystagmus with cross-coupling (i.e., horizontal head shaking causing inappropriate vertical nystagmus) occurs frequently. Overlap syndromes with peripheral vestibular disorders, such as cerebellar ataxia, neuropathy, and vestibular areflexia, exist rarely. Posturography and gait analysis can contribute to diagnostic differentiation, estimation of the risk of falls, as well as quantification of progression and treatment effects. Patients with cerebellar dizziness and vertigo should receive multimodal treatment, including balance training, occupational therapy, and medication.