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

2021 ◽  
pp. 088307382110283
Author(s):  
Adriana Brueggemann ◽  
Antonela Bicvic ◽  
Martina Goeldlin ◽  
Roger Kalla ◽  
Hassen Kerkeni ◽  
...  
Keyword(s):  
Ataxia Telangiectasia ◽  
Phase Ii Trial ◽  
Slow Phase ◽  
Central Position ◽  
Downbeat Nystagmus ◽  
The Gaze ◽  
Gaze Holding ◽  
Modifying Effect ◽  
Straight Ahead ◽  
Cerebellar Symptoms

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).

Three-Dimensional Eye Position and Slow Phase Velocity in Humans With Downbeat Nystagmus

2003 ◽  
Vol 89 (1) ◽  
pp. 338-354 ◽  
Author(s):  
S. Glasauer ◽  
M. Hoshi ◽  
U. Kempermann ◽  
T. Eggert ◽  
U. Büttner
Keyword(s):  
Brain Stem ◽  
Smooth Pursuit ◽  
Three Dimensional ◽  
Slow Phase ◽  
Downbeat Nystagmus ◽  
Gaze Holding ◽  
Fixation Task ◽  
Cerebellar Lesions ◽  
The Brain ◽  
Vestibular Pathways

Downbeat nystagmus (DN), a fixation nystagmus with the fast phases directed downward, is usually caused by cerebellar lesions, but the precise etiology is not known. A disorder of the smooth-pursuit system or of central vestibular pathways has been proposed. However, both hypotheses fail to explain why DN is usually accompanied by gaze-holding nystagmus, which implies a leaky neural velocity-to-position integrator. Because three-dimensional (3-D) analysis of nystagmus slow phases provides an excellent means for testing both hypotheses, we examined 19 patients with DN during a fixation task and compared them with healthy subjects. We show that the presentation of DN patients is not uniform; they can be grouped according to their deficits: DN with vertical integrator leakage, DN with vertical and horizontal integrator leakage, and DN without integrator leakage. The 3-D analysis of the slow phases of DN patients revealed that DN is most likely neither caused by damage to central vestibular pathways carrying semicircular canal information nor by a smooth pursuit imbalance. We propose that the observed effects can be explained by partial damage of a brain stem-cerebellar loop that augments the time constant of the neural velocity to position integrators in the brain stem and neurally adjusts the orientation of Listing's plane.

Gaze behavior of pre-adolescent children afflicted with Asperger Syndrome

2013 ◽  
Vol 9 (2) ◽  
pp. 173-186 ◽  
Author(s):  
Mari Wiklund
Keyword(s):  
Asperger Syndrome ◽  
Conversation Analysis ◽  
High Functioning Autism ◽  
Eye Contact ◽  
Nonverbal Behaviors ◽  
Gaze Behavior ◽  
High Functioning ◽  
The Gaze ◽  
In The Beginning ◽  
Straight Ahead

Asperger syndrome (AS) is a form of high-functioning autism characterized by qualitative impairment in social interaction. People afflicted with AS typically have abnormal nonverbal behaviors which are often manifested by avoiding eye contact. Gaze constitutes an important interactional resource, and an AS person’s tendency to avoid eye contact may affect the fluidity of conversations and cause misunderstandings. For this reason, it is important to know the precise ways in which this avoidance is done, and in what ways it affects the interaction. The objective of this article is to describe the gaze behavior of preadolescent AS children in institutional multiparty conversations. Methodologically, the study is based on conversation analysis and a multimodal study of interaction. The findings show that three main patterns are used for avoiding eye contact: 1) fixing one’s gaze straight ahead; 2) letting one’s gaze wander around; and 3) looking at one’s own hands when speaking. The informants of this study do not look at the interlocutors at all in the beginning or the middle of their turn. However, sometimes they turn to look at the interlocutors at the end of their turn. This proves that these children are able to use gaze as a source of feedback. When listening, looking at the speaker also seems to be easier for them than looking at the listeners when speaking.

scholarly journals Fixation eye movement abnormalities and stereopsis recovery following strabismus repair

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Talora L. Martin ◽  
Jordan Murray ◽  
Kiran Garg ◽  
Charles Gallagher ◽  
Aasef G. Shaikh ◽  
...  
Keyword(s):  
Eye Movements ◽  
Eye Movement ◽  
Functional Improvement ◽  
Slow Phase ◽  
Fixational Eye Movements ◽  
Movement Characteristics ◽  
Adaptive Mechanisms ◽  
Before And After ◽  
Gaze Holding ◽  
Fixational Saccades

AbstractWe 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.

Eye-Head Coordination during Optokinetic Stimulation in Squirrel Monkeys

1981 ◽  
Vol 90 (1) ◽  
pp. 85-88 ◽  
Author(s):  
Takeshi Kubo ◽  
David W. Jensen ◽  
Makoto Igarashi ◽  
Jerry L. Homick
Keyword(s):  
Statistical Analysis ◽  
Eye Movements ◽  
Negative Correlation ◽  
Guinea Pigs ◽  
Significant Negative Correlation ◽  
Squirrel Monkeys ◽  
Slow Phase ◽  
Optokinetic Stimulation ◽  
The Gaze ◽  
Significant Difference

Head and eye movements in the yaw plane were recorded during and after optokinetic stimulation in squirrel monkeys. 1) Phasic or tonic head deviations to the side of the ocular quick phase occurred in 94% of total recordings (n = 50) during the perstimulus period, and in 75% of recordings (n = 49) during the poststimulus period. Magnitude of mean head deviation was significantly different between perstimulus and poststimulus periods. 2) Head nystagmus associated with eye nystagmus was consistently observed in seven of nine squirrel monkeys during optokinetic stimulation. Squirrel monkeys are thereby less prone to display head nystagmus than either guinea pigs, pigeons or chickens. 3) Slow phase speeds of coupled head and eye nystagmus were subjected to statistical analysis. A highly significant negative correlation was found between slow phase head and eye speeds. The correlation coefficient was −0.81 at 60°/sec stimulus (n = 119) and −0.72 at 100°/sec stimulus (n = 131). The gaze speed, calculated by summing the head and eye speeds, was 59.1 ± 6.8/sec at 60°/sec and 92.2 ± 11.4 at 100°/sec stimulus. There was no significant difference between the gaze speed in a free head condition and the eye speed when the head was fixed.

Ictal downbeat nystagmus in Ménière disease

Neurology ◽  
2020 ◽  
Vol 95 (17) ◽  
pp. e2409-e2417
Author(s):  
Sun-Uk Lee ◽  
Hyo-Jung Kim ◽  
Jeong-Yoon Choi ◽  
Ji-Soo Kim
Keyword(s):  
Semicircular Canals ◽  
Vestibular Evoked Myogenic Potentials ◽  
Slow Phase ◽  
Downbeat Nystagmus ◽  
Meniere Disease ◽  
Head Impulse ◽  
Slow Phase Velocity ◽  
Ocular Reflex ◽  
Vestibulo Ocular Reflex ◽  
Menière Disease

ObjectiveTo determine the mechanism of ictal downbeat nystagmus in Ménière disease (MD), we compared the head impulse gain of the vestibulo-ocular reflex (VOR) for each semicircular canal between patients with (n = 7) and without (n = 70) downbeat nystagmus during attacks of MD.MethodsWe retrospectively analyzed the results of video-oculography, video head-impulse tests, and cervical vestibular-evoked myogenic potentials (VEMPs) in 77 patients with definite MD who were evaluated during an attack.ResultsPure or predominant downbeat nystagmus was observed in 7 patients (9%) with unilateral MD during the attacks. All 7 patients showed spontaneous downbeat nystagmus without visual fixation with a slow phase velocity ranging from 1.5 to 11.2°/s (median 5.4, interquartile range 3.7–8.5). All showed a transient decrease of the head impulse VOR gains for the posterior canals (PCs) in both ears (n = 4) or in the affected ear (n = 3). Cervical VEMPs were decreased in the affected (n = 2) or both ears (n = 2) when evaluated during the attacks. Downbeat nystagmus disappeared along with normalization of the VOR gains for PCs after the attacks in all patients. During the attacks, the head impulse VOR gains for the PC on the affected side were lower in the patients with ictal downbeat nystagmus than in those without (Mann-Whitney U test, p < 0.001), while the gains for other semicircular canals did not differ between the groups.ConclusionDownbeat nystagmus may be observed during attacks of MD due to an asymmetry in the vertical VOR or saccular dysfunction. MD should be considered in recurrent audiovestibulopathy and ictal downbeat nystagmus.

Nystagmus: Diagnosis, Topographic Anatomical Localization and Therapy

2021 ◽  
Vol 238 (11) ◽  
pp. 1186-1195
Author(s):  
Michael Leo Strupp ◽  
Dominik Straumann ◽  
Christoph Helmchen
Keyword(s):  
Eye Movements ◽  
Spontaneous Nystagmus ◽  
Downbeat Nystagmus ◽  
Blurred Vision ◽  
Primary Position ◽  
Ocular Motor Disorders ◽  
Gaze Holding ◽  
The One ◽  
Upbeat Nystagmus ◽  
Unilateral Vestibulopathy

AbstractNystagmus 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.

scholarly journals Conversion of upbeat to downbeat nystagmus in Wernicke encephalopathy

Neurology ◽  
2018 ◽  
Vol 91 (17) ◽  
pp. 790-796 ◽  
Author(s):  
Jorge C. Kattah ◽  
Ali Saber Tehrani ◽  
Sascha du Lac ◽  
David E. Newman-Toker ◽  
David S. Zee
Keyword(s):  
Thiamine Deficiency ◽  
Linear Acceleration ◽  
Selective Vulnerability ◽  
High Dose ◽  
Downbeat Nystagmus ◽  
Wernicke Encephalopathy ◽  
Truncal Ataxia ◽  
Gaze Holding ◽  
Ataxia Syndrome ◽  
Vertical Nystagmus

ObjectiveTo explain (1) why an initial upbeat nystagmus (UBN) converts to a permanent downbeat nystagmus (DBN) in Wernicke encephalopathy (WE) and (2) why convergence and certain vestibular provocative maneuvers may transiently switch UBN to DBN.MethodsFollowing a literature review and study of our 2 patients, we develop hypotheses for the unusual patterns of vertical nystagmus in WE.ResultsOur overarching hypothesis is that there is a selective vulnerability and a selective recovery from thiamine deficiency of neurons within brainstem gaze-holding networks. Furthermore, since the circuits affected in WE are commonly paraventricular, especially medially, just under the floor of the fourth ventricle where lie structures important for control of vertical gaze, we suggest the patterns of involvement in WE also reflect a breakdown in vulnerable areas of the blood–brain barrier. Many of the initial deficits of our patients improved over time, but their DBN did not. Irreversible changes in paramedian tract neurons, which project to the cerebellar flocculus, may be the cause. Here we suggest that conversion of UBN to permanent DBN points to thiamine deficiency and may argue for a chronic, nonprogressive DBN/truncal ataxia syndrome. Finally, we posit that the transient switch of UBN to DBN reflects abnormal processing of otolith information about linear acceleration, and often points to a diagnosis of WE.ConclusionRecognizing the unusual patterns of transient switching and then permanent conversion of UBN to DBN in WE is vital since long-term disability from WE may be prevented by timely, parenteral high-dose thiamine.

scholarly journals Three-Dimensional Eye-Head Coordination Is Implemented Downstream From the Superior Colliculus

2003 ◽  
Vol 89 (5) ◽  
pp. 2839-2853 ◽  
Author(s):  
Eliana M. Klier ◽  
Hongying Wang ◽  
J. Douglas Crawford
Keyword(s):  
Superior Colliculus ◽  
Three Dimensional ◽  
Slow Phase ◽  
Neural Basis ◽  
Gaze Shift ◽  
The Gaze ◽  
Listing's Law ◽  
Listing’S Law ◽  
Normal Behavior ◽  
The Brain

How the brain transforms two-dimensional visual signals into multi-dimensional motor commands, and subsequently how it constrains the redundant degrees of freedom, are fundamental problems in sensorimotor control. During fixations between gaze shifts, the redundant torsional degree of freedom is determined by various neural constraints. For example, the eye- and head-in-space are constrained by Donders' law, whereas the eye-in-head obeys Listing's law. However, where and how the brain implements these laws is not yet known. In this study, we show that eye and head movements, elicited by unilateral microstimulations of the superior colliculus (SC) in head-free monkeys, obey the same Donders' strategies observed in normal behavior (i.e., Listing's law for final eye positions and the Fick strategy for the head). Moreover, these evoked movements showed a pattern of three-dimensional eye-head coordination, consistent with normal behavior, where the eye is driven purposely out of Listing's plane during the saccade portion of the gaze shift in opposition to a subsequent torsional vestibuloocular reflex slow phase, such that the final net torsion at the end of each head-free gaze shift is zero. The required amount of saccade-related torsion was highly variable, depending on the initial position of the eye and head prior to a gaze shift and the size of the gaze shift, pointing to a neural basis of torsional control. Because these variable, context-appropriate torsional saccades were correctly elicited by fixed SC commands during head-free stimulations, this shows that the SC only encodes the horizontal and vertical components of gaze, leaving the complexity of torsional organization to downstream control systems. Thus we conclude that Listing's and Donders' laws of the eyes and head, and their three-dimensional coordination mechanisms, must be implemented after the SC.

Involvement of the receptors of the vestibular nucleus in the gaze-holding system of the cat

1994 ◽  
Vol 174 (2) ◽  
pp. 209-212 ◽  
Author(s):  
P. Mettens ◽  
G. Cheron ◽  
E. Godaux
Keyword(s):  
Vestibular Nucleus ◽  
The Gaze ◽  
Gaze Holding

scholarly journals Transitional nystagmus in a Bow Hunter’s Syndrome case report

BMC Neurology ◽  
2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Yasuyuki Nomura ◽  
Teruo Toi ◽  
Yasuo Ogawa ◽  
Takeshi Oshima ◽  
Yuichiro Saito
Keyword(s):  
Head Rotation ◽  
Final Diagnosis ◽  
Central Position ◽  
Downbeat Nystagmus ◽  
Video Record ◽  
First Case ◽  
Healthy Side ◽  
The Right ◽  
Cervical Diseases ◽  
Hunter's Syndrome

Abstract Background Bow Hunter’s Syndrome (BHS) is known as one of cervical diseases which causes vertigo, but the details of its vertigo, especially nystagmus and eye movement, are still incompletely understood. This time, we reported the first case of BHS with a nystagmus chart with video record of transitional nystagmus. Case presentation The patient, a 47-year-old female, complained of vertigo caused by head rotation. When she turned her head leftward, leftward nystagmus appeared, and this was followed by dullness of the right arm. After her head was returned to the central position, downbeat nystagmus appeared, which changed to rightward nystagmus. She was diagnosed with BHS by her symptoms and images. We recorded a nystagmus video and nystagmus chart of this transitional nystagmus including downbeat nystagmus. Her vertigo was cured by the modification of a prescription for her past medical history: hypertension. Conclusion The vertigo of BHS accompanies nystagmus. In this present case, the transitional nystagmus was observed, and it occurred toward the healthy side. Then the nystagmus direction was changed to the affected side via downbeat nystagmus. This is the first report with both a nystagmus chart with video of BHS. Nowadays, various kinds of vertigo induced by neck movement are known. BHS is a rare disease among vertigo diseases, but we should consider it as a different diagnosis of vertigo patients. A precise interview and proper examination are required to make the final diagnosis.

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