Functional impact of bilateral vestibular loss and the unexplained complaint of oscillopsia.

Introduction: The vestibulo-ocular reflex (VOR) stabilizes vision during head movements. VOR disorders lead to symptoms such as imbalance, dizziness, and oscillopsia. Despite similar VOR dysfunction, patients display diverse complaints. This study analyses saccades, balance, and spatial orientation in chronic peripheral and central VOR disorders, specifically examining the impact of oscillopsia. Methods: Participants involved 15 patients with peripheral bilateral vestibular loss (pBVL), 21 patients with clinically and genetically confirmed Machado-Joseph disease (MJD) who also have bilateral vestibular deficit, and 22 healthy controls. All pBVL and MJD participants were tested at least 9 months after the onset of symptoms and underwent a detailed clinical neuro-otological evaluation at the Dizziness and Eye Movements Clinic of the Meir Medical Center. Results: Among the 15 patients with pBVL and 21 patients with MJD, only 5 patients with pBVL complained of chronic oscillopsia while none of the patients with MJD reported this complaint. Comparison between groups exhibited significant differences in vestibular, eye movements, balance, and spatial orientation. When comparing oscillopsia with no-oscillopsia subjects, significant differences were found in the dynamic visual acuity test, the saccade latency of eye movements, and the triangle completion test. Discussion: Even though there is a significant VOR gain impairment in MJD with some subjects having less VOR gain than pBVL with reported oscillopsia, no individuals with MJD reported experiencing oscillopsia. This study further supports that subjects experiencing oscillopsia present a real impairment to stabilize the image on the retina, whereas those without oscillopsia may utilize saccade strategies to cope with it and may also rely on visual information for spatial orientation. Finding objective differences will help to understand the causes of the oscillopsia experience and develop coping strategies to overcome it.

Bilateral vestibulopathy as the initial presentation of CANVAS.

Cerebellar ataxia with neuropathy and vestibular areflexia syndrome (CANVAS) is a slowly progressing autosomal recessive ataxic disorder linked to an abnormal biallelic intronic (most commonly) AAGGG repeat expansion in the replication factor complex subunit 1 (RFC1). While the clinical diagnosis is relatively straightforward when the three components of the disorder are present, it becomes challenging when only one of the triad (cerebellar ataxia, neuropathy or vestibular areflexia) manifests. Isolated cases of Bilateral Vestibulopathy (BVP) or vestibular areflexia that later developed the other components of CANVAS have not been documented. We report four cases of patients with chronic imbalance and BVP that, after several years, developed cerebellar and neuropathic deficits with positive genetic testing for RFC1. Our report supports the concept that CANVAS should be considered in every patient with BVP of unknown etiology, even without the presence of the other triad components. This is especially important given that about 50% of cases in many BVP series are diagnosed as idiopathic, some of which may be undiagnosed CANVAS.

The vestibular symptomatology of Machado-Joseph Disease.

BACKGROUND: Machado Joseph Disease (MJD) is an autosomal dominant neurodegenerative disease. In previous studies, we described significant bilateral horizontal Vestibulo-Ocular Reflex (VOR) deficit within this population without any reference to the presence of vestibular symptomatology. OBJECTIVE: To evaluate whether, beyond cerebellar ataxia complaints, MJD patients have typical vestibular symptomatology corresponding to the accepted diagnostic criteria of Bilateral Vestibulopathy (BVP) according to the definition of the International Barany Society of Neuro-Otology. METHODS: Twenty-one MJD, 12 clinically stable chronic Unilateral Vestibulopathy (UVP), 15 clinically stable chronic BVP, and 22 healthy Controls underwent the video Head Impulse Test (vHIT) evaluating VOR gain and filled out the following questionnaires related to vestibular symptomatology: The Dizziness Handicap Inventory (DHI), the Activities-specific Balance Confidence Scale (ABC), the Vertigo Visual Scale (VVS) and the Beck Anxiety Inventory (BAI). RESULTS: The MJD group demonstrated significant bilateral vestibular impairment with horizontal gain less than 0.6 in 71% of patients (0.54±0.17). Similar to UVP and BVP, MJD patients reported a significantly higher level of symptoms than Controls in the DHI, ABC, VVS, and BAI questionnaires. CONCLUSIONS: MJD demonstrated significant VOR impairment and clinical symptoms typical of BVP. We suggest that in a future version of the International Classification of Vestibular Disorders (ICVD), MJD should be categorized under a separate section of central vestibulopathy with the heading of bilateral vestibulopathy. The present findings are of importance regarding the clinical diagnosis process and possible treatment based on vestibular rehabilitation.

[THE HIDDEN VESTIBULAR FEATURES OF MACHADO JOSEPH DISEASE (SPINOCEREBELLAR ATAXIA 3)].

INTRODUCTION: Machado-Joseph disease (MJD) is an inherited neurodegenerative disease with progressive cerebellar ataxia manifested through lack of coordination and balance. MJD patients also present significant Vestibulo-Ocular Reflex (VOR) deficit but their whole vestibular features have not been previously evaluated. We aimed to evaluate whether MJD patients have vestibular features fitting the diagnostic criteria of Bilateral Vestibulopathy established by the International Society for Neuro-otology. METHODS: Sixteen MJD patients and 21 healthy controls underwent a detailed clinical neuro-otological examination including a quantitative evaluation of the VOR gain using the video Head Impulse Test (vHIT). Vestibular-related symptoms were evaluated by the Dizziness Handicap Inventory (DHI), the Activities-specific Balance Confidence Scale (ABC), the Vertigo Visual Scale (VVS). In addition, anxiety that is frequently present in vestibular disorders, was evaluated by the Beck Anxiety Inventory (BAI). RESULTS: MJD patients had significantly reduced horizontal VOR gain with significantly higher scores in all vestibular-related symptoms questionnaires. These symptoms scores were like those reported in studies evaluating patients with bilateral peripheral vestibular loss. CONCLUSIONS: Beyond the cerebellar deficits, MJD patients have vestibular signs and symptoms fitting the diagnostic criteria of Bilateral Vestibulopathy established by the International Society for Neuro-otology. These findings are of relevance not only for the diagnosis and evaluation of progressive cerebellar diseases but also for the possible beneficial effect of vestibular rehabilitation techniques on dizziness, balance and the emotional, physiological and functional aspects of MJD.

The overarching effects of vestibular deficit: Imbalance, anxiety, and spatial disorientation.

BACKGROUND: Comorbid Balance, Anxiety, and Spatial symptoms are observed in neurodevelopmental disorders and aging. Each of these symptoms was studied separately in association with vestibular hypofunction. We aimed to investigate whether such a diffuse range of symptoms has common vestibular pathophysiology. Specifically, we tested whether this Triad of dysfunctions is associated with central or peripheral vestibular hypofunction. We also assessed the possible contribution of semicircular canals (SCCs) vs. saccular function. METHODS: We tested patients with Peripheral bilateral and unilateral Vestibular Hypofunction (PVH), Machado Joseph Disease (MJD) with cerebellar and central bilateral vestibular hypofunction, and healthy controls. SCCs and sacculi functioning were evaluated by the video Head Impulse Test (vHIT) and cervical Vestibular Evoked Myogenic Potentials (cVEMP), respectively. Balance was assessed by the Activities-specific Balance Confidence scale (ABC), anxiety by the Hamilton Anxiety Rating Scale (HAM-A), and spatial orientation by the Object Perspective Taking test (OPT-t). RESULTS: PVH patients with vestibular SCCs and saccular hypofunction presented the Triad of symptoms, imbalance, anxiety, and spatial disorientation. MJD patients with SCCs-related vestibular hypofunction but preserved saccular-related vestibular function presented with a partial profile of imbalance and spatial disorientation. CONCLUSIONS: The present study provides evidence that peripheral vestibular hypofunction is associated with the Triad of dysfunctions, i.e., imbalance, anxiety, and spatial disorientation. The combination of SCCs and saccular hypofunction seems to contribute to the emergence of the Triad of symptoms.

Horizontal Vestibulo-Ocular Reflex Deficit as a Biomarker for Clinical Disease Onset, Severity, and Progression of Machado-Joseph Disease.

Because of the crucial importance of finding a useful biomarker for further clinical trials in Machado-Joseph disease (MJD), and based on our previous studies, we aimed to evaluate whether the horizontal vestibulo-ocular reflex (VOR) gain could be a reliable neurophysiological biomarker for the clinical onset, severity, and progression of the disease. Thirty-five MJD patients, 11 pre-symptomatic genetically confirmed MJD subjects, and 20 healthy controls underwent a detailed epidemiological and clinical neurological examination including the Scale for the Assessment and Rating of Ataxia (SARA). Their VOR gain was measured using the video Head Impulse Test system. Twenty of the MJD patients were re-tested after a period of 1-3 years. Horizontal VOR gain was abnormal in 92% of MJD, 54% pre-symptomatic, and 0% healthy controls. Horizontal VOR gain in the MJD group was significantly negatively correlated with SARA score in the first (r=0.66, p<0.001) and second (r=0.61, p<0.001) examinations. There was also a significant negative correlation between the percentage of change in horizontal VOR gain and the percentage of change in SARA score across both examinations (r=-0.54, p < 0.05). A regression model of the SARA score with the horizontal VOR gain and disease duration as predictors demonstrated that both the horizontal VOR gain and the disease duration had an independent contribution to the prediction of the SARA score. The horizontal VOR gain seems to be a reliable biomarker for the clinical onset, severity, and progression of MJD and could be used in further clinical studies.

"I Do Not Know How You Feel and How I Feel About That": Mentalizing Impairments in Machado-Joseph Disease.

Machado Joseph disease (MJD), also known as spinocerebellar ataxia type 3 (SCA3), is an autosomal dominant neurodegenerative disease. Mentalizing is the ability to think and understand the mental state of the other and of the self in terms of thoughts, feelings, and intentions. The aim of this study is to fill the gap in our understanding of mentalizing in MJD since there is currently very little and inconsistent research on MJD and mentalizing. A total of 18 Jews of Yemenite origin with clinically and genetically confirmed MJD, 5 pre-symptomatic MJD with a positive genetic test, and 17 Jews of Yemenite origin healthy controls, underwent a battery of tests consisting of reading the mind in the eyes (RME), Toronto Alexithymia Scale (TAS-20), and false belief test (FBt). The MJD group scored lower on the RME and FBt, and higher on TAS-20 test compared to control. A significant negative correlation was found between disease duration and RME score. All the pre-symptomatic participants scored within the normal clinical range in all tests. MJD patients demonstrated a widespread deficiency in the ability to mentalizing on a clinical level with autistic characteristics. These impairments may impact the patient's interpsychic experience and daily life interactions and have important clinical implication. Pre-symptomatic participants demonstrated normal mentalizing in all tests, suggesting that the mentalizing impairments do not precede the symptoms of ataxia and are part of the clinical picture of MJD.

How vestibular dysfunction transforms into symptoms of depersonalization and derealization?

BACKGROUND: Psychiatric Depersonalization/Derealization (DPDR) symptoms were demonstrated in patients with peripheral vestibular disorders. However, only semicircular canals (SCCs) dysfunction was evaluated, therefore, otoliths' contribution to DPDR is unknown. Also, DPDR symptoms in patients with central vestibular dysfunction are presently unknown. DPDR was also studied in the context of spatial disorientation and anxiety, but the relation of these cognitive and emotional functions to vestibular dysfunction requires clarification. METHODS: We tested patients with peripheral Bilateral Vestibular Hypofunction (pBVH), Machado Joseph Disease (MJD) with cerebellar and central bilateral vestibular hypofunction, and healthy controls. Participants completed the video Head Impulse Test (vHIT) for SCCs function, cervical Vestibular Evoked Myogenic Potentials test (cVEMPt) for sacculi function, Body Sensation Questionnaire (BSQ) for panic anxiety, Object Perspective-Taking test (OPTt) for spatial orientation and Cox & Swinson DPDR inventory for DPDR symptoms. RESULTS: pBVH patients showed significant SCCs and sacculi dysfunction, spatial disorientation, elevated panic anxiety, and DPDR symptoms. MJD patients showed significant SCCs hypofunction but preserved sacculi function, spatial disorientation but normal levels of panic anxiety and DPDR symptoms. Only pBVH patients demonstrated a positive correlation between the severity of the DPDR and spatial disorientation and panic anxiety. CONCLUSIONS: DPDR develops in association with sacculi dysfunction, either with or without SSCs dysfunction. Spatial disorientation and anxiety seem to mediate the transformation of vestibular dysfunction into DPDR symptoms. DPDR does not develop in MJD with central vestibular hypofunction but a normal saccular response. We propose a three-step model that describes the development of DPDR symptoms in vestibular patients.

The rediscovered motor-related area 55b emerges as a core hub of music perception.

Passive listening to music, without sound production or evident movement, is long known to activate motor control regions. Nevertheless, the exact neuroanatomical correlates of the auditory-motor association and its underlying neural mechanisms have not been fully determined. Here, based on a NeuroSynth meta-analysis and three original fMRI paradigms of music perception, we show that the long-ignored pre-motor region, area 55b, an anatomically unique and functionally intriguing region, is a core hub of music perception. Moreover, results of a brain-behavior correlation analysis implicate neural entrainment as the underlying mechanism of area 55b's contribution to music perception. In view of the current results and prior literature, area 55b is proposed as a keystone of sensorimotor integration, a fundamental brain machinery underlying simple to hierarchically complex behaviors. Refining the neuroanatomical and physiological understanding of sensorimotor integration is expected to have a major impact on various fields, from brain disorders to artificial general intelligence.

Angular vestibulo ocular reflex loss with preserved saccular function in Machado-Joseph disease.

OBJECTIVE: To provide a comprehensive evaluation of the vestibular function in Machado-Joseph Disease (MJD). METHODS: 21 MJD patients and 19 healthy Controls underwent a detailed clinical neuro-otological evaluation including VOR gain of all six semicircular canals by video Head Impulse Test (vHIT), remaining horizontal VOR function by Suppression Head Impulse test (SHIMP), and saccular function by cervical Vestibular Evoked Myogenic Potentials (cVEMP). RESULTS: All MJD had significantly lower VOR gain in all six semicircular canals (p < 0.001) with a mean ± SEM of horizontal gain of 0.52 ± 0.04 and vertical gain of 0.57 ± 0.03 versus Controls' gain of 0.95 ± 0.01 and 0.81 ± 0.02, respectively (p < 0.001). MJD showed also a significantly lower VOR gain on the SHIMP test with left gain of 0.51 ± 0.04 and right gain of 0.46 ± 0.03 versus Controls' gain of 0.79 ± 0.01 and 0.83 ± 0.03, respectively (p < 0.001). In contrast, MJD had normal saccular function reflected by the presence of cVEMP response in 18/20 patients and in 12/17 of Controls, with a non-significant difference between MJD and Controls of P13 and N23 peaks latency and normalized peak-to-peak amplitude. ROC analysis of horizontal VOR gain resulted in an area under the curve of 0.993 making the average lateral canals' VOR gain an excellent classifier of MJD vs Controls. CONCLUSIONS: Horizontal and vertical VOR impairment with preserved sacculo-collic function seems to be a distinctive feature of MJD and could be explained by selective, mostly medial and superior vestibular nuclei degeneration. This study further supports the idea that horizontal VOR gain measured by vHIT could be a potential neurophysiological biomarker of MJD.

Trehalose in Machado-Joseph Disease: Safety, Tolerability, and Efficacy.

Machado-Joseph disease (MJD) is relatively prevalent among the Yemenite Jewish subpopulation living in Israel. Currently, there is no treatment able to modify the disease progression. Trehalose is a disaccharide with protein-stabilizing and autophagy-enhancing properties. In animal models of MJD, trehalose showed reduction of cerebellar lesion size and improved motor function. This study was designed to be a proof-of-concept, phase 2 study lasting 6 to 12 months, to determine the safety, tolerability, and efficacy of weekly IV administration of 15 g or 30 g 10% trehalose solution in 14 MJD patients. Primary endpoints were safety and tolerability, which were assessed by various clinical and laboratory tests. Secondary endpoints were changes in the Scale for Assessment and Rating of Ataxia (SARA) score, Neurological Examination Score for Spinocerebellar Ataxia (NESSCA), time to do 9-hole peg test (9HPT), time to do 8-meter walk (8MW), and quality of life assessed by the World Health Organization Quality-of-Life Questionnaire-BREF (WHOQoL-BREF). Trehalose was well tolerated, and no serious drug-related adverse events were noted. The average SARA score, NESSCA, and time to do 9HPT and 8MW and the WHOQoL-BREF for all patients remained stable at 6 months. Six patients received treatment for as long as 12 months and continued to remain stable on all the above tests. IV trehalose seems to be safe in humans and probably effective to stabilize neurological impairment in MJD.

Selective Procedural Memory Impairment but Preserved Declarative Memory in Spinocerebellar Ataxia Type 3.

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is an autosomal dominant neurodegenerative disorder that affects mainly the cerebellum and less other brain areas. While the ataxic/motor features of the disease have been well described, the cognitive consequences of the degeneration require additional testing. The aim of this study was to evaluate learning abilities in SCA3. We tested 13 SCA3 patients and 14 age-matched healthy controls, all of Yemenite origin, on a neuropsychological battery of procedural and declarative memory tests. SCA3 patients demonstrated impaired sequence learning on the procedural Serial Reaction Time test (SRTt) but normal learning on the procedural Weather Prediction Probabilistic Classification test (WPPCt). SCA3 patients showed normal learning on the declarative Rey Auditory Verbal Learning test (Rey-AVLt). The correlations between the learning measures of the SRTt, WPPCt, and Rey-AVLt tests in SCA3 and controls separately were not significant. These results imply that the cerebellar degeneration in SCA3 causes selective impairment in procedural sequence learning while the procedural probabilistic learning and declarative memory were mostly preserved. These findings support the assumption that procedural learning is not a homogeneous function and could be dissociated in cerebellar neurodegenerative disease.

Is there a prediction network? Meta-analytic evidence for a cortical-subcortical network likely subserving prediction.

Predictive coding is an increasingly influential and ambitious concept in neuroscience viewing the brain as a 'hypothesis testing machine' that constantly strives to minimize prediction error, the gap between its predictions and the actual sensory input. Despite the invaluable contribution of this framework to the formulation of brain function, its neuroanatomical foundations have not been fully defined. To address this gap, we conducted activation likelihood estimation (ALE) meta-analysis of 39 neuroimaging studies of three functional domains (action perception, language and music) inherently involving prediction. The ALE analysis revealed a widely distributed brain network encompassing regions within the inferior and middle frontal gyri, anterior insula, premotor cortex, pre-supplementary motor area, temporoparietal junction, striatum, thalamus/subthalamus and the cerebellum. This network is proposed to subserve domain-general prediction and its relevance to motor control, attention, implicit learning and social cognition is discussed in light of the predictive coding scheme. Better understanding of the presented network may help advance treatments of neuropsychiatric conditions related to aberrant prediction processing and promote cognitive enhancement in healthy individuals.

Yemenite-Jewish families with Machado-Joseph disease (MJD/SCA3) share a recent common ancestor.

In 1994, a kindred from Yemen was described as the first Jewish family with Machado-Joseph disease (MJD/SCA3), a dominant ataxia caused by the expansion of a (CAG)n above 61 repeats, in ATXN3. MJD is spread worldwide due to an ancient variant of Asian origin (the Joseph lineage). A second, more recent, independent expansion arose in a distinct haplotype (Machado lineage); other possible origins are still under study. We haplotyped 46 MJD patients and relatives, from 6 Israeli Yemenite families, and 100 normal chromosomes from that population, for 30 SNPs spreading 15 kb around the (CAG)n, and 8 STRs and 1 indel in the flanking regions. All six families shared an extended haplotype, showing no variants or recombination after a common origin, but differing in two SNPs (rs12895357 and rs12588287) from the Joseph lineage. To test for a new mutational origin in this population, we searched for the presence of that haplotype in Yemenite-Jewish controls. Only one (1%) normal (CAG)32 allele showed an extended STR-haplotype genetically closer to MJD than normal haplotypes (genetic distance, DA, 0.43 versus 0.53). That normal allele could be explained either by (1) the introduction of both normal and expanded alleles carrying this "Joseph-like" haplotype into the genetic pool of the Yemenite population; or by (2) a large contraction from the expanded CAG range. Based on the lack of STR diversity in MJD Yemenite-Jewish families, and on high frequency of this Joseph-like haplotype among African controls (23.2%), expanded alleles seem to have been introduced very recently (<400 years ago) from Africa.

Opsoclonus myoclonus ataxia associated with West Nile virus infection: A dramatic presentation with benign prognosis?

Opsoclonus myoclonus and ataxia is a combination of severe neurological signs associated with several pathologic agents and conditions. Only few cases of opsoclonus have been related to West Nile virus infection. We report on a 61-year-old woman and on a 55-year-old man who had history of recent fever, who were hospitalized because of acute severe truncal ataxia, opsoclonus and tremor with minimal myoclonic jerks. A through work-up revealed the presence of both IgM and IgG antibodies against West Nile virus both in the serum and Cerebrospinal Fluid and excluded other causes known to be associated with this combination of neurological signs. The first case was treated with corticosteroids, followed by significant improvement, and the second recovered spontaneously. The acute combination of opsoclonus, severe truncal ataxia and tremor with a history of recent fever requires, during the relevant season and in the relevant geographic area, a search for a recent infection with West Nile virus. Though initially suffering from a devastating sickness, our patients eventually recovered.

Spinocerebellar ataxia type 3 in Israel: phenotype and genotype of a Jew Yemenite subpopulation.

Spinocerebellar ataxia type 3 is an autosomal dominant ataxia with various phenotypes affecting Jews of Yemenite origin in Israel. Clinical and family pedigrees data of 125 Yemenite Jewish patients were collected in our clinic. All examined patients underwent a detailed neurological and bedside vestibular examination. Cytosine-adenine-guanine repeats size in the Ataxin-3 gene was measured, and patients with expanded cytosine-adenine-guanine repeats >44 were diagnosed genetically as having spinocerebellar ataxia type 3. We estimated a disease prevalence rate of about 29/100,000 in Jew of Yemenite descendents living in Israel. We were able to group patients into 17 families. Mean age of onset was 44 years. 74 % of our population expressed neurological signs compatible with sub-phenotype III, i.e., ataxia and polyneuropathy. Vestibulo-ocular reflex deficit detected on bedside examination was found in 90 % of the patients. The mean number of cytosine-adenine-guanine repeats in the Ataxin-3 gene of the diseased allele was 67 (range 55-76). Age of onset was inversely correlated with the number of cytosine-adenine-guanine repeats (r = -0.7) and was significantly earlier among male patients. Though the mean number of cytosine-adenine-guanine repeats was not larger in the offspring, their age of onset was significantly earlier than that of their parents. In addition, paternal offspring expressed the disease significantly earlier than maternal offspring. Signs and stages of disease seem to progress slower during the first 10-15 years of the disease and faster afterward. A high disease prevalence rate in our Yemenite Jewish subpopulation is similar to that found in other isolated populations in other countries. Vestibulo-ocular reflex deficit detected on bedside examination should be added as part of the phenotype of Yemenite Jewish patients. Our clinical and genetic findings are in partial agreement with other spinocerebellar ataxia type 3 population studies and are relevant to patient management and the design of further studies.

Noncontrast Brain Computed Tomography Findings of Spontaneous Intracranial Hypotension in the Emergency Department Setting.

BACKGROUND: Spontaneous intracranial hypotension (SIH) is a difficult diagnosis, especially in an emergency department (ED) setting where magnetic resonance imaging (MRI) is usually not available. OBJECTIVES: To emphasize the presence of a very frequent but unnoticed tentorial subdural hygroma among a number of recognized noncontrast brain computed tomography (CT) findings in patients with spontaneous intracranial hypotension. METHODS: This is a case series study of 7 consecutive patients with orthostatic headache who were admitted to the ED and finally diagnosed as SIH, and of 11 women who underwent brain CT due to very severe orthostatic headache after epidural anesthesia. We evaluated the CT findings of patients with SIH and further compared each patient's CT findings with their respective MRI and with the brain CT of women with postepidural anesthesia orthostatic headache. RESULTS: Noncontrast brain CT was abnormal in five out of seven (71%) SIH cases: tentorial subdural hygroma was found in four (57%) cases; supratentorial subdural hygroma and cervical spinal venous engorgement were found in two (29%) cases, and subdural hematoma was found in one case. All women with severe orthostatic headache after epidural anesthesia had CT findings similar to those of spontaneous intracranial hypotension patients. CONCLUSIONS: The presence of a tentorial subdural hygroma on brain CT in a patient with orthostatic headache may strongly suggest the diagnosis of intracranial hypotension. This finding can be of high clinical significance in an emergency setting, avoiding additional invasive or expensive procedures.

Impaired vestibulo-ocular reflex (VOR) in spinocerebellar ataxia type 3 (SCA3): bedside and search coil evaluation.

Vestibulo-Ocular Reflex (VOR) abnormalities in cerebellar ataxias are a matter of renewed interest. We have previously reported vestibular areflexia in a group of Yemenite-Jews with Spinocerebellar Ataxia Type 3 (SCA3) who had clear bilateral pathological horizontal Head Impulse Test (HIT). The objective of this study was to evaluate the VOR of ten SCA3 patients who have variable bedside HIT responses by recording their eye movements using magnetic search coils and to correlate these results with their clinical and genetic data. Eight out of the ten patients have abnormal horizontal HIT detected by both clinical bedside examination and laboratory tests. Results of bedside HIT testing were significantly correlated with the VOR gain recorded using magnetic search coils. No significant correlations were found between VOR gain and other clinical or genetic data. Our study confirms the presence of defective VOR in SCA3 patients and corroborates the useful of the HIT as a reliable bedside test for diagnosis of VOR deficits.

Multiple saccadic abnormalities in spinocerebellar ataxia type 3 can be linked to a single deficiency in velocity feedback.

PURPOSE: The purpose of the current research is to understand if the different eye movement abnormalities in patients with the same neurologic disease are related to varied disease processes or, alternately, do different patients adopt different strategies to overcome a singular brain deficiency. METHODS: Using a magnetic search coil, we measured saccade dynamics, that is position and velocity waveforms, for patients diagnosed with spinocerebellar ataxia type 3 (SCA-3), also known as Machado-Joseph disease (MJD). RESULTS: We observed that the saccadic waveform of the majority of the SCA-3 patients (7 of 10) exhibited dynamic overshoot, with the eye passing the desired endpoint and making a rapid correction before coming to rest. Patients with normal waveforms, that is with no dynamic overshoot, had saccades with relatively low peak velocity. CONCLUSIONS: Velocity feedback in a closed loop control system is essential for providing a fast response without overshoot. Lack of a velocity feedback or an imbalance between position and velocity gains yields a tradeoff between response time and overshoot. While the goal of a saccade is to get to the desired position, models based on animal research suggest that the saccadic control also incorporates a velocity feedback. Results presented here indicated that all SCA-3 patients had deviations in the saccadic waveform, albeit of two types, either slow saccades or dynamic overshooting saccades. Using saccadic models based on animal research can explain how a single deficit, that is a mismatched velocity control of the motor error due to the disease, can yield these two different abnormalities in human patients.