BackgroundPatients with downbeat nystagmus syndrome suffer from oscillopsia, which leads to an unstable visual perception and therefore impaired visual acuity. The aim of this study was to use real-time computer-based visual feedback to compensate for the destabilizing slow phase eye movements.MethodsThe patients were sitting in front of a computer screen with the head fixed on a chin rest. The eye movements were recorded by an eye tracking system (EyeSeeCam®). We tested the visual acuity with a fixed Landolt C (static) and during real-time feedback driven condition (dynamic) in gaze straight ahead and (20°) sideward gaze. In the dynamic condition, the Landolt C moved according to the slow phase eye velocity of the downbeat nystagmus. The Shapiro-Wilk test was used to test for normal distribution and one-way ANOVA for comparison.ResultsTen patients with downbeat nystagmus were included in the study. Median age was 76 years and the median duration of symptoms was 6.3 years (SD +/- 3.1y). The mean slow phase velocity was moderate during gaze straight ahead (1.44°/s, SD +/- 1.18°/s) and increased significantly in sideward gaze (mean left 3.36°/s; right 3.58°/s). In gaze straight ahead, we found no difference between the static and feedback driven condition. In sideward gaze, visual acuity improved in five out of ten subjects during the feedback-driven condition (p = 0.043).ConclusionsThis study provides proof of concept that non-invasive real-time computer-based visual feedback compensates for the SPV in DBN. Therefore, real-time visual feedback may be a promising aid for patients suffering from oscillopsia and impaired text reading on screen. Recent technological advances in the area of virtual reality displays might soon render this approach feasible in fully mobile settings.
Bilateral vestibulopathy (BVP) is defined as the impairment or loss of function of either the labyrinths or the eighth nerves. Patients with total BVP due to bilateral vestibular nerve section exhibit difficulties in spatial memory and navigation and show a loss of hippocampal volume. In clinical practice, most patients do not have a complete loss of function but rather an asymmetrical residual functioning of the vestibular system. The purpose of the current study was to investigate navigational ability and hippocampal atrophy in BVP patients with residual vestibular function. Fifteen patients with BVP and a group of age- and gender- matched healthy controls were examined. Self-reported questionnaires on spatial anxiety and wayfinding were used to assess the applied strategy of wayfinding and quality of life. Spatial memory and navigation were tested directly using a virtual Morris Water Maze Task. The hippocampal volume of these two groups was evaluated by voxel-based morphometry. In the patients, the questionnaire showed a higher spatial anxiety and the Morris Water Maze Task a delayed spatial learning performance. MRI revealed a significant decrease in the gray matter mid-hippocampal volume (Left: p = 0.006, Z = 4.58, Right: p < 0.001, Z = 3.63) and posterior parahippocampal volume (Right: p = 0.005, Z = 4.65, Left: p < 0.001, Z = 3.87) compared to those of healthy controls. In addition, a decrease in hippocampal formation volume correlated with a more dominant route-finding strategy. Our current findings demonstrate that even partial bilateral vestibular loss leads to anatomical and functional changes in the hippocampal formation and objective and subjective behavioral deficits.
The diagnosis of bilateral vestibulopathy (BV) is typically established based on bilateral semicircular canal dysfunction. The degree to which both otolith organs—the saccule and utricle—are also impaired in BV is not wellestablished, particularly with respect to the etiology and severity of BV. The aim of this study was to evaluate semicircular canal, saccular and utricular function in patients with BV due to aminoglycoside ototoxicity and bilateral Menière’s disease, and with different severities of BV. Caloric and head impulse testing were used as measures of canal function. Cervical vestibular-evoked myogenic potentials (cVEMP) and ocular VEMPs (oVEMP) were used as measures of saccular and utricular function, respectively. We enrolled 34 patients with BV and 55 controls in a prospective case–control study. Patients with BV were less likely to have saccular (61 %) or utricular (64 %) dysfunction relative to canal dysfunction (100 %). Utricular function differed significantly between patients by etiologic group: the poorest function was found in patients with BV due to aminoglycoside toxicity, and the best function in Menière’s disease patients. Canal and saccular function did not vary according to etiology. Further, utricular but not saccular function was significantly correlated with canal function. Saccular and utricular function had the strongest association with Dizziness Handicap Inventory scores relative to canal function. These data suggest that when a patient with BV is identified in a clinical context, oVEMP testing is the most sensitive test in distinguishing between aminoglycoside toxicity and bilateral Menière’s disease. Both cVEMP and oVEMP testing may be considered to evaluate the functional impact on the patient.
An impairment of eye movements, or nystagmus, is seen in many diseases of the central nervous system, in particular those affecting the brainstem and cerebellum, as well as in those of the vestibular system. The key to diagnosis is a systematic clinical examination of the different types of eye movements, including: eye position, range of eye movements, smooth pursuit, saccades, gaze-holding function and optokinetic nystagmus, as well as testing for the different types of nystagmus (e.g., central fixation nystagmus or peripheral vestibular nystagmus). Depending on the time course of the signs and symptoms, eye movements often indicate a specific underlying cause (e.g., stroke or neurodegenerative or metabolic disorders). A detailed knowledge of the anatomy and physiology of eye movements enables the physician to localize the disturbance to a specific area in the brainstem (midbrain, pons or medulla) or cerebellum (in particular the flocculus). For example, isolated dysfunction of vertical eye movements is due to a midbrain lesion affecting the rostral interstitial nucleus of the medial longitudinal fascicle, with impaired vertical saccades only, the interstitial nucleus of Cajal or the posterior commissure; common causes with an acute onset are an infarction or bleeding in the upper midbrain or in patients with chronic progressive supranuclear palsy (PSP) and Niemann–Pick type C (NP-C). Isolated dysfunction of horizontal saccades is due to a pontine lesion affecting the paramedian pontine reticular formation due, for instance, to brainstem bleeding, glioma or Gaucher disease type 3; an impairment of horizontal and vertical saccades is found in later stages of PSP, NP-C and Gaucher disease type 3. Gaze-evoked nystagmus (GEN) in all directions indicates a cerebellar dysfunction and can have multiple causes such as drugs, in particular antiepileptics, chronic alcohol abuse, neurodegenerative cerebellar disorders or cerebellar ataxias; purely vertical GEN is due to a midbrain lesion, while purely horizontal GEN is due to a pontomedullary lesion. The pathognomonic clinical sign of internuclear ophthalmoplegia is an impaired adduction while testing horizontal saccades on the side of the lesion in the ipsilateral medial longitudinal fascicule. The most common pathological types of central nystagmus are downbeat nystagmus (DBN) and upbeat nystagmus (UBN). DBN is generally due to cerebellar dysfunction affecting the flocculus bilaterally (e.g., due to a neurodegenerative disease). Treatment options exist for a few disorders: miglustat for NP-C and aminopyridines for DBN and UBN. It is therefore particularly important to identify treatable cases with these conditions.
Twenty-one days of restraint stress has been shown to affect hippocampal plasticity, neurogenesis, and spatial memory. Hippocampal glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) are the main mediators of stress response and learning/memory processes. We studied the performance of male and female rats on a hippocampal-dependent spatial task after 21 days of restraint in relation to the stress-induced changes of GR and MR status in their hippocampi. Reduced GR immunostaining was detected in the dentate gyrus and CA1 area of stressed male rats. Stressed male rats performed worse than the male control rats on the Morris water maze. In contrast, unaltered (in the dentate gyrus) or increased (in CA1) GR immunoreactivity was seen in the hippocampus of stressed female rats. Stressed female rats had an improved memory score in the task compared with the female control rats. In addition, stressed female rats showed increased MR immunostaining in the CA3 area, which is known to be severely affected by stress. The observed sexually dimorphic effects of 21-day restraint in spatial learning and memory may be associated with the sex-dependent changes in hippocampal corticosteroid receptor status after stress.
Cervical and ocular vestibular-evoked myogenic potential (cVEMP/oVEMP) tests are widely used clinical tests of otolith function. However, VEMP testing may not be the ideal measure of otolith function given the significant inter-individual variability in responses and given that the stimuli used to elicit VEMPs are not physiological. We therefore evaluated linear motion perceptual threshold testing compared with cVEMP and oVEMP testing as measures of saccular and utricular function, respectively. A multi-axis motion platform was used to measure horizontal (along the inter-aural and nasooccipital axes) and vertical motion perceptual thresholds. These findings were compared with the vibration-evoked oVEMP as a measure of utricular function and soundevoked cVEMP as a measure of saccular function. We also considered how perceptual threshold and cVEMP/ oVEMP testing are each associated with Dizziness Handicap Inventory (DHI) scores. We enrolled 33 patients with bilateral vestibulopathy of different severities and 42 controls to have sufficient variability in otolith function. Subjects with abnormal oVEMP amplitudes had significantly higher (poorer) perceptual thresholds in the inter-aural and naso-occipital axes in age-adjusted analyses; no significant associations were observed for vertical perceptual thresholds and cVEMP amplitudes.Both oVEMP amplitudes and naso-occipital axis perceptual thresholds were significantly associated with DHI scores. These data suggest that horizontal perceptual thresholds and oVEMPs may estimate the same underlying physiological construct: utricular function.
Vertigo and dizziness are with a life-time prevalence of ~30% among the most common symptoms and are often associated with nystagmus or other oculomotor disorders. The prerequisite for a successful treatment is a precise diagnosis of the underlying disorder. In this overview, the current pharmacological treatment options for peripheral and central vestibular, cerebellar, and oculomotor disorders including nystagmus are described. There are basically seven groups of drugs that can be used (the "7 As"): antiemetics; anti-inflammatory, anti-Menière's, and antimigraine medications; antidepressants, anticonvulsants, and aminopyridines. In acute vestibular neuritis, recovery of the peripheral vestibular function can be improved by treatment with oral corticosteroids. In Menière's disease, a long-term high-dose treatment with betahistine-dihydrochloride (at least 48 mg three times daily) had a significant effect on the frequency of the attacks; the underlying mode of action is evidently an increase in inner-ear blood flow. The use of aminopyridines is a well-established therapeutic principle in the treatment of downbeat and upbeat nystagmus as well as episodic ataxia type 2 and cerebellar gait disorders. As was shown in animal experiments, these potassium channel blockers increase the activity and excitability and normalize irregular firing of cerebellar Purkinje cells. They evidently augment the inhibitory influence of these cells on vestibular and deep cerebellar nuclei. A few studies showed that baclofen improves periodic alternating nystagmus; gabapentin and memantine improve pendular and infantile nystagmus. However, many other eye-movement disorders such as ocular flutter, opsoclonus, central positioning, and see-saw nystagmus are still difficult to treat. Although substantial progress has been made, further state-of-the-art trials must still be performed on many vestibular and oculomotor disorders, namely Menière's disease, vestibular paroxysmia, vestibular migraine, and many forms of central eye-movement disorders.
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