Oculomotor and Vestibular Findings in Gaucher Disease Type 3 and Their Correlation with Neurological Findings

Bremova-Ertl, Tatiana; Schiffmann, Raphael; Patterson, Marc C.; Belmatoug, Nadia; Villemeur, Thierry Billette de; Bardins, Stanislavs; Frenzel, Claudia; Malinová, Věra; Naumann, Silvia; Arndt, Juliane; Mengel, Eugen; Reinke, Jörg; Strobl, Ralf; Strupp, Michael

doi:10.3389/fneur.2017.00711

Cited by 26 publications

(35 citation statements)

References 32 publications

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“…This study was undertaken to evaluate the use of video-oculography as a tool to measure saccadic eye movement parameters in Gaucher Disease. We have replicated the previously reported data showing lower peak velocity in horizontal and vertical saccadic eye movements in nGD patients versus a control cohort [13,17,23,24]; although the specific values in the cohort are slightly higher than those reported by Bremova-Ertl et al [17] the difference between the values is consistent. The ability to replicate data findings between disease states is supportive of a role for such a device for clinical use.…”

Section: Discussionsupporting

confidence: 91%

“…The stimulus protocol was adapted from Bremova-Ertl and colleagues [17] and comprised a calibration sequence followed by visually-guided reflexive prosaccades. All participants were instructed to re-fixate to the new target spot as rapidly and as accurately as possible and to withhold any unwanted gaze shifts.…”

Section: Recording Of Eye Movementsmentioning

confidence: 99%

“…Here we report on the experience in the UK of measuring saccadic eye movements using videooculography (EyeSeeCam) in Gaucher Patients with type 1 and type 3 disease. We evaluated 60 patients and 29 healthy controls with a view to replicating the previously reported slowing of saccadic movements in patients with neuronopathic disease [17], evaluating the role of longitudinal analysis for disease monitoring and outcome measure development and examining the role of such a device in supporting diagnosis of neuronopathic disease. For comparison, healthy controls (n=35, age years, range 23-59 years) were recruited from a single research centre.…”

Section: Introductionmentioning

confidence: 99%

“…The modified Severity Scoring Tool (mSST)[32] was designed and implemented as a clinical tool for this purpose and has shown utility, however a component of the tool includes saccadic eye movement deficits and the cohort presented here with objective measures with neuronopathic disease was small. Correlation has been demonstrated with vertical saccade duration and mSST previously[17,23] but a larger cohort study is required and ideally a more detailed scoring tool or biomarker to demonstrate CNS involvement.LimitationsA larger cohort of control data confirming any subtly differences in saccade parameters by age would be of value. Observations from this cohort of controls may not have been adequately powered to demonstrate significant statistical difference by age; however previous studies (using various devices to measure saccadic movements) have shown that with increasing age, peak saccade velocity is reduced…”

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confidence: 99%

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Eye Movement Biomarkers Allow for the Definition of Phenotypes in Gaucher Disease

Donald

Tan

Chakrapani

et al. 2020

Preprint

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Background Neurological forms of Gaucher disease, the inherited disorder of b-Glucosylceramidase caused by bi-allelic variants in GBA1, is a progressive disorder which lacks a disease-modifying therapy. Systemic manifestations of disease are effectively treated with Enzyme Replacement Therapy (ERT), however, molecules which cross the blood-brain barrier are still under investigation. Clinical trials of such therapeutics require robust, reproducible clinical endpoints to demonstrate efficacy and clear phenotypic definitions to identify suitable patients for inclusion in trials. The single consistent clinical feature in all patients with neuronopathic disease is the presence of a supranuclear saccadic gaze palsy, in the presence of Gaucher disease this finding serves as diagnostic of ‘type 3’ Gaucher disease. MethodsWe undertook a study to evaluate saccadic eye movements in Gaucher patients and to assess the role of the EyeSeeCam in measuring saccades. The EyeSeeCam is a video oculography device which was used to run a protocol of saccade measures. We studied 39 patients with non-neurological Gaucher disease (type 1), 21 patients with type 3 (neurological) disease and a series of 35 healthy controls. Mean saccade parameters were compared across disease subgroups. ResultsWe confirmed the saccadic abnormality in patients with type 3 Gaucher disease andidentified an unexpected subgroup of patients with type 1 Gaucher disease who demonstrated significant saccade parameter abnormalities. These patients also showed subtle neurological findings and shared aGBA1 variant. ConclusionsThis striking novel finding of a potentially attenuated type 3 Gaucher phenotype associated with a specific GBA1 variant and detectable saccadic abnormality prompts review of current disease classification. Further, this finding highlights the broad spectrum of neuronopathic Gaucher phenotypes relevant when designing inclusion criteria for clinical trials.

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Section: Discussionsupporting

confidence: 91%

Section: Recording Of Eye Movementsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mentioning

confidence: 99%

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Eye Movement Biomarkers Allow for the Definition of Phenotypes in Gaucher Disease

Donald

Tan

Chakrapani

et al. 2020

Preprint

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“…However, certain patterns of SCC deficits and catch-up saccade characteristic should still prove helpful. Recent studies have highlighted a number of disorders that can present with combined central and peripheral lesions: AICA strokes and cerebellopontine angle (CPA) tumor ( 7 , 23 ), metabolic disorders such as Gaucher disease(GD) ( 8 , 46 ) and Wernicke encephalopathy ( 10 , 47 ), and cerebellar degeneration ( 9 , 48 , 49 ). By far, over 70% are accounted for by AICA stroke and CPA tumor ( 45 ).…”

Section: Combined Central and Peripheral Vestibular Lesionsmentioning

confidence: 99%

Central Lesions With Selective Semicircular Canal Involvement Mimicking Bilateral Vestibulopathy

Chen

Hálmagyi

2018

Front. Neurol.

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Bilateral vestibulopathy (BVP), which is due to peripheral lesions, may selectively involve certain semicircular canal (SCC). Recent eye movement recordings with search coil and video head impulse test (HIT) have provided insight in central lesions that can cause bilateral and selective SCC deficit mimicking BVP. Since neurological signs or ocular motor deficits maybe subtle or absent, it is critical to recognize central lesions correctly since there is prognostic and treatment implication. Acute floccular lesions cause bilateral horizontal SCC (HC) impairment while leaving vertical SCC function unaffected. Vestibular nuclear lesions affect bilateral HC and posterior SCC (PC) function, but anterior SCC (AC) function is spared. When both eyes are recorded, medial longitudinal fasciculus lesions cause horizontal dysconjugacy in HC function and catch-up saccades, as well as selective deficiency of PC over AC function. Combined peripheral and central lesions may be difficult to distinguish from BVP. Anterior inferior cerebellar artery stroke causes two types of deficits: 1. ipsilateral pan-SCC deficits and contralateral HC deficit and 2. bilateral HC deficit with vertical SCC sparing. Metabolic disorders such as Wernicke encephalopathy characteristically involve HC but not AC or PC function. Gaucher disease causes uniform loss of all SCC function but with minimal horizontal catch-up saccades. Genetic cerebellar ataxias and cerebellar-ataxia neuropathy vestibular areflexia syndrome typically do not spare AC function. While video HIT does not replace the gold-standard, search coil HIT, clinicians are now able to rapidly and accurately identify specific pattern of SCC deficits, which can aid differentiation of central lesions from BVP.

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The definition of neuronopathic Gaucher disease

Schiffmann¹,

Sevigny²,

Rolfs

et al. 2020

J of Inher Metab Disea

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Neuronopathic Gaucher disease (nGD) has a very wide clinical and genotypic spectrum. However, there is no consensus definition of nGD, including no description of how best to diagnostically separate the acute form—Gaucher type 2—from the subacute or chronic form—Gaucher type 3. In this article, we define the various forms of Gaucher disease with particular emphasis on the presence of gaze palsy in all patients with nGD. This consensus definition will help in both clinical diagnosis and appropriate patient recruitment to upcoming clinical trials.

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Oculomotor and Vestibular Findings in Gaucher Disease Type 3 and Their Correlation with Neurological Findings

Cited by 26 publications

References 32 publications

Eye Movement Biomarkers Allow for the Definition of Phenotypes in Gaucher Disease

Eye Movement Biomarkers Allow for the Definition of Phenotypes in Gaucher Disease

Central Lesions With Selective Semicircular Canal Involvement Mimicking Bilateral Vestibulopathy

The definition of neuronopathic Gaucher disease

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