Spatial orientation in patients with chronic unilateral vestibular hypofunction is ipsilesionally distorted

OBJECTIVE Acute unilateral peripheral-vestibular hypofunction (UVH) shifts the subjective visual vertical (SVV) ipsilesionally, triggering central compensation that usually eliminates shifts when upright. We hypothesized that compensation is worse when roll-tilted. METHODS We quantified SVV errors and variability in different roll-tilted positions (0°, ±45°, ±90°) in patients with chronic UVH affecting the superior branch (SVN; n=4) or the entire (CVN; n=9) vestibular nerve. RESULTS Errors in SVN and CVN were not different. When roll-tilted ipsilesionally 45° (9.6±5.4° vs. -0.2±6.4°, patients vs. controls, p<0.001) and 90° (23.5±5.7° vs. 16.8±8.8°, p=0.003), the patient's SVV was shifted significantly towards the lesioned ear. When upright, only a trend was noted (3.6±2.2° vs. 0.0±1.2°, p=0.099); for contralesional roll-tilts shifts were not different from controls. Variability was larger for CVN than SVN (p=0.046). With increasing disease-duration, adjustment errors decayed for ipsilesional roll-tilt and upright (p⩽0.025). CONCLUSIONS The reason verticality perception was distorted for ipsilesional roll-tilts, may be the insufficient integration of contralesional otolith-input. Similar errors in SVN and CVN suggest a dominant utricular role in verticality perception, albeit the sacculus may improve precision of SVV estimates. SIGNIFICANCE With deficiencies in central compensation being roll-angle dependent, extending SVV-testing to roll-tilted positions may improve identifying patients with chronic UVH

Pitfalls in the diagnostic evaluation of subacute combined degeneration

We report a case of a 43-year-old man presenting with a 2-week history of painless ascending sensory disturbances, suspected to be suffering from acute inflammatory polyneuropathy. On clinical examination, deep tendon reflexes were preserved and muscle strength was 5/5 everywhere. Gait was ataxic with positive Romberg test. Lumbar puncture was normal and electroneurography demonstrated demyelination. With spinal cord involvement centred on the posterior tracts on MRI, differential diagnosis focused on cobalamin deficiency. Initial laboratory work up showed nearly normal holotranscobalamin (43 pmol/L, normal>50) suggesting no vitamin B12 deficiency. Surprisingly, further testing including methylmalonic acid (3732 nmol/L, normal<271) and homocysteine (48.5 µmol/L, normal<10) showed an impairment of vitamin B12-dependent metabolism leading to the diagnosis of subacute combined degeneration. Only after repeated history taking did the patient remember having taken tablets containing cobalamin for 3 days before hospitalisation. In case of B12 deficiency, holotranscobalamin can rapidly normalise during supplementation, whereas methylmalonic acid and homocysteine might help to detect B12 deficiency in patients who recently started supplementation

Visually guided adjustments of body posture in the roll plane

Body position relative to gravity is continuously updated to prevent falls. Therefore, the brain integrates input from the otoliths, truncal graviceptors, proprioception and vision. Without visual cues estimated direction of gravity mainly depends on otolith input and becomes more variable with increasing roll-tilt. Contrary, the discrimination threshold for object orientation shows little modulation with varying roll orientation of the visual stimulus. Providing earth-stationary visual cues, this retinal input may be sufficient to perform self-adjustment tasks successfully, with resulting variability being independent of whole-body roll orientation. We compared conditions with informative (earth-fixed) and non-informative (body-fixed) visual cues. If the brain uses exclusively retinal input (if earth-stationary) to solve the task, trial-to-trial variability will be independent from the subject's roll orientation. Alternatively, central integration of both retinal (earth-fixed) and extra-retinal inputs will lead to increasing variability when roll-tilted. Subjects, seated on a motorized chair, were instructed to (1) align themselves parallel to an earth-fixed line oriented earth-vertical or roll-tilted 75° clockwise; (2) move a body-fixed line (aligned with the body-longitudinal axis or roll-tilted 75° counter-clockwise to it) by adjusting their body position until the line was perceived earth-vertical. At 75° right-ear-down position, variability increased significantly (p<0.05) compared to upright in both paradigms, suggesting that, despite the earth-stationary retinal cues, extra-retinal input is integrated. Self-adjustments in the roll-tilted position were significantly (p<0.01) more precise for earth-fixed cues than for body-fixed cues, underlining the importance of earth-stable visual cues when estimates of gravity become more variable with increasing whole-body rol

Vestibulo-cerebellar disease impairs the central representation of self-orientation

Transformation of head-fixed otolith signals into a space-fixed frame of reference is essential for perception of self-orientation and ocular motor control. In monkeys the nodulus and ventral uvula of the vestibulo-cerebellum facilitate this transformation by computing an internal estimate of direction of gravity. These experimental findings motivated the hypothesis that degeneration of the vestibulo-cerebellum in humans alter perceptual and ocular motor functions that rely on accurate estimates of gravity, such as subjective visual vertical (SVV), static ocular counterroll (OCR), and gravity-dependent modulation of vertical ocular drifts. We assessed the SVV, OCR, and spontaneous vertical ocular drifts in 12 patients with chronic vestibulo-cerebellar disease and in 10 controls. Substantially increased variability in estimated SVV was noted in the patients. Furthermore, gravity-dependent modulation of spontaneous vertical ocular drifts along the pitch plane was significantly (p < 0.05) larger in the patients. However, the gain and variability of static OCR and errors in SVV were not significantly different. In conclusion, in chronic vestibulo-cerebellar disease SVV and OCR remain intact except for an abnormal variability in the perception of verticality and impaired stabilization of gaze mediated by the otoliths. These findings suggest that OCR and perceived vertical are relatively independent from the cerebellum unless there is a cerebellar imbalance like an acute unilateral cerebellar stroke. The increased trial-to-trial SVV variability may be a general feature of cerebellar disease since a function of the cerebellum may be to compensate for such. SVV variability might be useful to monitor disease progression and treatment response in patients

Neurobiological mechanisms of acute vertigo

The vestibular system provides us with reflexive responses of eye movements and balance control, as well as with perceptual estimates of self-motion and gravity direction. Crucial to its proper functioning is a bilaterally balanced vestibular signal originating from the vestibular end organs in the inner ears and projecting via vestibular nerve afferents to the brainstem vestibular nuclei. Disturbances of the bilateral vestibular interplay become evident in cases of acute unilateral peripheral vestibular deafferentation. The resultant sudden imbalance of vestibular afferent tone at the level of the vestibular nuclei leads to pronounced ocular–motor and postural impairment, as well as to intensive vertigo and/or dizziness, accompanied by autonomic symptoms, such as nausea and vomiting. Subsequent compensatory mechanisms efficiently diminish these static symptoms (such as spontaneous nystagmus) within days and allow functional recovery of dynamic symptoms (such as blurred vision during fast head turns) to such a degree that most patients return to their normal daily activities within weeks. This article aims to provide an understanding about the pathophysiological changes after unilateral vestibular deafferentation and the current knowledge on the compensatory mechanisms

Clival Chondrosarcoma Associated With an Intra-Axial Cystic Medullary Lesion Responsive to Steroids

Introduction: Here we present a 75-year-old patient who was admitted with acute-onset right-sided hemiparesis, dysphagia, dysarthria and nystagmus. Repeated MRI scans showed two lesions with contact to one another: one solid stationary extra-axial lesion at the caudal part of the clivus and a rapidly growing intra-axial cystic lesion at the level of the medulla oblongata. Biopsy of the solid lesion demonstrated a low-grade chondrosarcoma, while no tissue sample of the cystic lesion could be retrieved. After initiation of dexamethasone therapy the cystic lesion markedly regressed.Background: A literature search on published cases with the same combination of a stationary solid extra-axial mass at the caudal part of the clivus and a growing intra-axial cystic mass in the medulla oblongata was negative, indicating that the case described here is both unique and novel.Discussion: Considering the rapid progression of symptoms and growth on MR-imaging in combination with the marked response to steroids, an inflammatory response linked to the chondrosarcoma is most likely. At the same time other possible explanations as a second neoplasm, an abscess or an ischemic lesion seem unlikely.Concluding remarks: This case underlines an unusual complication of a rare brainstem tumor and outlines both the differential diagnosis and potential treatment options. For such cystic lesions in combination with chondrosarcoma, a treatment course with steroids should be considered along with surgical exploration necessary to obtain the diagnosis and for potential reduction of mass-effect on the medulla oblongata

Hypertrophy of the Inferior Olivary Nucleus Impacts Perception of Gravity

Interruption of the dentato-olivary projections, interconnecting the dentate nucleus (DN) and the contralateral inferior olivary nucleus (ION), is predicted to interfere with the DN’ role in estimating direction of gravity. In a patient with pendular nystagmus due to hypertrophy of the ION secondary to predominantly right-sided ponto-mesencephalic hemorrhage, perceived vertical shifted from clockwise to counter-clockwise deviations within 4 months. We hypothesize that synchronized oscillations of ION neurons induce a loss of inhibitory control, leading to hyperactivity of the contralateral DN and, as a result, to perceived vertical roll–tilt to the side of the over-active DN

Editorial: Bilateral Vestibulopathy - Current Knowledge and Future Directions to Improve its Diagnosis and Treatment

Many patients with bilateral vestibulopathy experience chronic oscillopsia due to failure of the vestibulo-ocular reflex and gait instability due to failure of vestibulo-spinal reflexes. There are numerous potential contributing factors, however, many cases remain idiopathic. The diagnosis of bilateral vestibulopathy is often delayed, placing patients at risk for unnecessary diagnostic tests and late initiation of treatment. Novel diagnostic tests offer new opportunities to characterize patterns of vestibular impairment. With the advent of new therapies, there is urgency to define and better understand patients with bilateral vestibulopathy. This collection includes topics such as an exploration of the large class of patients with bilateral vestibulopathy currently considered idiopathic, by identifying novel pathophysiologic mechanisms. Other topics include a historical perspective on early recognition, the impact of bilateral vestibular impairment on quality of life, and how advances in diagnostics are refining our understanding of what it means to have bilateral vestibulopathy. New developments in treatment strategies for patients with bilateral vestibulopathy are also featured