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Monocular torsional eye oscillations are a rare form of disconjugate nystagmus and the underlying pathophysiology is not well understood. Here, we present and discuss a case with disabling torsional oscillopsia in one eye only. The patient exhibited (i) spontaneous pendular torsional nystagmus of the left eye and (ii) rhythmic involuntary movements of the soft palate and uvula, consistent with the syndrome of oculopalatal tremor with monocular nystagmus. Brain MRI revealed an infarct of the left dentate nucleus in the cerebellum and, more caudally, a secondary hypertrophic degeneration of the right inferior olivary nucleus. To account for the presence of torsional nystagmus on the eye contralateral to the side of inferior olivary hypertrophy and ipsilateral to the lesioned dentate nucleus, we discuss the hypothesis of a (inferior olivary nucleus-mediated) malfunctioning adaptation of the anterior canal vestibulo-ocular reflex. [ABSTRACT FROM AUTHOR]

Oculomotor deficits are common in hereditary ataxia, but disproportionally neglected in clinical ataxia scales and as outcome measures for interventional trials. Quantitative assessment of oculomotor function has become increasingly available and thus applicable in multicenter trials and offers the opportunity to capture severity and progression of oculomotor impairment in a sensitive and reliable manner. In this consensus paper of the Ataxia Global Initiative Working Group On Digital Oculomotor Biomarkers, based on a systematic literature review, we propose harmonized methodology and measurement parameters for the quantitative assessment of oculomotor function in natural-history studies and clinical trials in hereditary ataxia. MEDLINE was searched for articles reporting on oculomotor/vestibular properties in ataxia patients and a study-tailored quality-assessment was performed. One-hundred-and-seventeen articles reporting on subjects with genetically confirmed (n=1134) or suspected hereditary ataxia (n=198), and degenerative ataxias with sporadic presentation (n=480) were included and subject to data extraction. Based on robust discrimination from controls, correlation with disease-severity, sensitivity to change, and feasibility in international multicenter settings as prerequisite for clinical trials, we prioritize a core-set of five eye-movement types: (i) pursuit eye movements, (ii) saccadic eye movements, (iii) fixation, (iv) eccentric gaze holding, and (v) rotational vestibulo-ocular reflex. We provide detailed guidelines for their acquisition, and recommendations on the quantitative parameters to extract. Limitations include low study quality, heterogeneity in patient populations, and lack of longitudinal studies. Standardization of quantitative oculomotor assessments will facilitate their implementation, interpretation, and validation in clinical trials, and ultimately advance our understanding of the evolution of oculomotor network dysfunction in hereditary ataxias. [ABSTRACT FROM AUTHOR]

Long-term deficits of the vestibulo-ocular reflex (VOR) elicited by head rotation can be partially compensated by catch-up saccades (CuS). These saccades are initially visually guided, but their latency can greatly decrease resulting in short latency CuS (SL-CuS). It is still unclear what triggers these CuS and what are the underlying neural circuits. In this study, we aimed at evaluating the impact of cerebellar pathology on CuS by comparing their characteristics between two groups of patients with bilateral vestibular hypofunction, with or without additional cerebellar dysfunction. We recruited 12 patients with both bilateral vestibular hypofunction and cerebellar dysfunction (BVH-CD group) and 12 patients with isolated bilateral vestibular hypofunction (BVH group). Both groups were matched for age and residual VOR gain. Subjects underwent video head impulse test recording of the horizontal semicircular canals responses as well as recording of visually guided saccades in the step, gap, and overlap paradigms. Latency and gain of the different saccades were calculated. The mean age for BVH-CD and BVH was, respectively, 67.8 and 67.2 years, and the mean residual VOR gain was, respectively, 0.24 and 0.26. The mean latency of the first catch-up saccade was significantly longer for the BVH-CD group than that for the BVH group (204 ms vs 145 ms, p < 0.05). There was no significant difference in the latency of visually guided saccades between the two groups, for none of the three paradigms. The gain of covert saccades tended to be lower in the BVH-CD group than in BVH group (t test; p = 0.06). The mean gain of the 12° or 20° visually guided saccades were not different in both groups. Our results suggest that the cerebellum plays a role in the generation of compensatory SL-CuS observed in BVH patients. [ABSTRACT FROM AUTHOR]

This document, titled "Ocular Flutter Evoked by Vestibular Stimulation," discusses a case study of a 26-year-old woman who experienced ocular flutter, a condition characterized by spontaneous bursts of eye movements, exclusively during head motion and vestibular stimulation. The patient presented with oscillopsia (the perception of objects moving) and other symptoms such as clumsiness and headache. Various tests and examinations were conducted, including video-oculography, which revealed the presence of ocular flutter during specific stimuli. The authors propose several mechanisms that may explain the occurrence of ocular flutter in this case, involving the interaction between the vestibular and saccadic systems. The patient's symptoms improved after receiving treatment with intravenous immunoglobulin and methylprednisolone. The study suggests that vestibular stimulation may play a role in generating ocular flutter. [Extracted from the article]

In 1967, Andén, Fuxe, and Ungerstedt demonstrated the presence of monoamine-containing fibers in the rat cerebellum. Over the past 50 years, this finding has provided clinical relevance of the noradrenergic system to the cerebellum. Cerebellar dysfunction and noradrenergic system may relate to tremor in Parkinson disease and essential tremor, motor learning, and the vestibulo–ocular reflex in spinocerebellar ataxias. Cognition and emotion may also be linked to the cerebellar noradrenergic system, in relation to the symptoms of Alzheimer disease, dementia with Lewy bodies, and attention-deficit/hyperactivity disorder. Despite recent technological advances in neuroimaging for evaluating the noradrenergic system, we need more evidence to understand the precise pathophysiological relationship between the cerebellum and the noradrenergic system and its clinical implications. [ABSTRACT FROM AUTHOR]

The article discusses a case study of a 57-year-old man with multiple system atrophy (MSA) presenting with ocular flutter triggered specifically by vestibular stimulation, alongside various neurological symptoms including gait difficulty, oscillopsia, and dysarthria. It highlights the diagnostic challenges and neurological manifestations associated with MSA, emphasizing the role of vestibular and ocular motor deficits in differentiating this condition from other neurodegenerative disorders.

1 Schematic diagram of the pathophysiological mechanisms underlying anti-VGCC, anti-mGluR1, and anti-GluR delta-associated cerebellar ataxias ("LTDpathies"). Basal synaptic transmission is impaired not only by anti-VGCC Abs but also by anti-mGluR1 and GluR delta Abs [[24]]. These studies suggest that anti-VGCC, anti-mGluR1, and anti-GluR delta Abs-associated cerebellar ataxias share one common pathophysiological mechanism, the deregulated PF-PC LTD. In IMCAs, various synaptic proteins, such as glutamic acid decarboxylase 65 (GAD65), voltage-gated Ca channel (VGCC), metabotropic glutamate receptor type 1 (mGluR1), and glutamate receptor delta (GluR delta), are targets of auto-immunity [[14]-[16]]. [Extracted from the article]

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a recently described slowly progressive ataxia with severe imbalance due to the compromise of three of the four sensory inputs for balance, leaving only vision unaffected. Bilateral vestibulopathy is present but saccular and utricular function, measured by vestibular evoked myogenic potentials (VEMPs), has not been widely studied in these patients. Dysautonomia has been reported but is not among the diagnostic criteria. We performed a database analysis to identify patients evaluated between 2003 and 2019 with probable diagnosis of CANVAS by using key words "bilateral vestibulopathy and/or cerebellar ataxia and/or sensory polyneuropathy." Five out of 842 met all conditions. Patients underwent neurological/neurootological exam, brain MRI, visually enhanced vestibulo-ocular reflex (VVOR) exam by high-speed video-oculography using video-Head Impulse Test (vHIT), VEMPs, neurophysiological studies, and genetic tests to exclude other causes of ataxia. Dysautonomia was addressed by the standardized survey of autonomic symptoms. All patients had clinically definite CANVAS as brain MRI showed vermal cerebellar atrophy, neurophysiological studies showed a sensory neuronopathy pattern (absent sensory action potentials), VVOR was abnormal bilaterally, and genetic tests ruled out other causes of ataxia including SCA 3 and Friedreich ataxia. Patients had at least 3 dysautonomic symptoms, including xerostomia/xerophthalmia (5/5). VEMP results varied among patients, ranging from normal to completely abnormal. We found inconsistent results with VEMPs. The utilization of VEMPs in more CANVAS cases will determine its utility in this syndrome. Dysautonomia may be included in the diagnostic criteria. [ABSTRACT FROM AUTHOR]

The Y-group plays an important role in the generation of upward smooth pursuit eye movements and contributes to the adaptive properties of the vertical vestibulo-ocular reflex. Malfunction of this circuitry may cause eye movement disorders, such as downbeat nystagmus. To characterize the neuron populations in the Y-group, we performed immunostainings for cellular proteins related to firing characteristics and transmitters (calretinin, GABA-related proteins and ion channels) in brainstem sections of macaque monkeys that had received tracer injections into the oculomotor nucleus. Two histochemically different populations of premotor neurons were identified: The calretinin-positive population represents the excitatory projection to contralateral upgaze motoneurons, whereas the GABAergic population represents the inhibitory projection to ipsilateral downgaze motoneurons. Both populations receive a strong supply by GABAergic nerve endings most likely originating from floccular Purkinje cells. All premotor neurons express nonphosphorylated neurofilaments and are ensheathed by strong perineuronal nets. In addition, they contain the voltage-gated potassium channels Kv1.1 and Kv3.1b which suggests biophysical similarities to high-activity premotor neurons of vestibular and oculomotor systems. The premotor neurons of Y-group form a homogenous population with histochemical characteristics compatible with fast-firing projection neurons that can also undergo plasticity and contribute to motor learning as found for the adaptation of the vestibulo-ocular reflex in response to visual-vestibular mismatch stimulation. The histochemical characterization of premotor neurons in the Y-group allows the identification of the homologue cell groups in human, including their transmitter inputs and will serve as basis for correlated anatomical-neuropathological studies of clinical cases with downbeat nystagmus. [ABSTRACT FROM AUTHOR]

The syndrome of cerebellar ataxia with neuropathy and bilateral vestibular areflexia (CANVAS) has emerged progressively during the last 30 years. It was first outlined by the neurootology/neurophysiology community in the vestibular areflexic patients, through the description of patients slowly developing late-onset cerebellar ataxia and bilateral vestibulopathy. The characteristic deficit of visuo-vestibulo-ocular reflex (VVOR) due to the impaired slow stabilizing eye movements was put forward and a specific disease subtending this syndrome was suggested. The association to a peripheral sensory axonal neuropathy was described later on, with neuropathological studies demonstrating that both sensory neuropathy and vestibular areflexia were diffuse ganglionopathy. Clinical and electrophysiological criteria of CANVAS were then proposed in 2016. Besides the classical triad, frequent chronic cough, signs of dysautonomia and neurogenic pains were frequently observed. From the beginning of published cohorts, sporadic as well as familial cases were reported, the last suggestive of an autosomal recessive mode of transmission. The genetic disorder was discovered in 2019, under the form of abnormal biallelic expansion in the replication factor C subunit 1 (RFC1) in a population of late-onset ataxia. This pathological expansion was found in 100% of the familial form and 92% of sporadic ones when the triad was complete. But using the genetic criteria, the phenotype of CANVAS seems to expand, for exemple including patients with isolated neuronopathy. We propose here to review the clinical, electrophysiological, anatomical, genetic aspect of CANVAS in light of the recent discovery of the genetic aetiology, and discuss differential diagnosis, neuropathology and physiopathology. [ABSTRACT FROM AUTHOR]

The bedside examination associated with their clinical history remains the most critical means to accurately diagnose the cause for most of the signs and symptoms related to pathology of the cerebellum and vestibular system in patients presenting with dizziness and imbalance. This paper focuses on those critical bedside examinations, suggests when laboratory testing might be useful to confirm the clinical suspicion, and considers the shared neural circuitry within the visual and vestibular systems to offer an algorithmic approach in conducting the clinical bedside examination. [ABSTRACT FROM AUTHOR]

In clinical practice, the head impulse test paradigm (HIMP) and the suppression head impulse paradigm (SHIMP) stimulate high-frequency head movements so that the visual system is temporarily suppressed. The two tests could also be useful tools for vestibular assessment at low frequencies: VVOR (visually enhanced vestibulo-ocular reflex) and VORS (vestibulo-ocular reflex suppression). The aim of this study is to analyze the eye movements typically found during VVOR and VORS testing in patients with unilateral and bilateral vestibular hypofunction. Twenty patients with unilateral vestibular hypofunction, three patients with bilateral vestibular hypofunction, and ten patients with normal vestibular function (control group) were analyzed through VVOR and VORS testing with an Otometrics ICS Impulse system. During the VVOR test, patients with unilateral vestibular hypofunction exhibited corrective saccades to the same direction of the nystagmus fast phase toward the healthy side when the head rotates toward the affected side, while patients with bilateral vestibular hypofunction exhibited corrective saccades to the opposite side of head movements to each side. During the VORS test, patients with unilateral vestibular hypofunction seem to exhibit larger corrective saccades to the healthy side when the head was moved to this side, while patients with bilateral vestibular hypofunction did not exhibit corrective saccades during head movements to either side. Our data suggest that the VVOR and VORS tests yield the same diagnostic information as the HIMP and SHIMP tests in unilateral and bilateral vestibular hypofunction, and can contribute to the diagnosis of a peripheral vestibular loss as well as the affected side. [ABSTRACT FROM AUTHOR]

108122 7 Waespe W, Cohen B, Raphan T. Role of the flocculus and paraflocculus in optokinetic nystagmus and visual-vestibular interactions: effects of lesions. A decade later, Raphan and Cohen lesioned the macaque cerebellar nodulus and ventral uvula, prolonging the velocity storage time constant [[6]]. A redundant multisensory signal is necessary for accurate motion perception and vestibulo-ocular reflex (VOR). [Extracted from the article]