Saccadic Impairments in Patients with the Norrbottnian Form of Gaucher’s Disease Type 3

Blume, Josefine; Beniaminov, Stanislav; Björkvall, Cecilia Kämpe; Machaczka, Maciej; Svenningsson, Per

doi:10.3389/fneur.2017.00295

Cited by 9 publications

(19 citation statements)

References 16 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: 90%

“…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: 90%

mentioning

confidence: 99%

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

Donald

Tan

Chakrapani

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…The modified Severity Scoring Tool (mSST) [38] 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 [18,24] but a larger cohort study is required and ideally a more detailed scoring tool or biomarker to demonstrate CNS involvement.…”

Section: Discussionmentioning

confidence: 99%

Eye movement biomarkers allow for the definition of phenotypes in Gaucher Disease

Donald

Tan

Chakrapani

et al. 2020

Preprint

View full text Add to dashboard Cite

Background Neurological forms of Gaucher disease, the inherited disorder of β-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. Methods We 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. Results We confirmed the saccadic abnormality in patients with type 3 Gaucher disease and identified 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 a GBA1 variant. Conclusions This 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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“…Ocular motor apraxia, which in fact reflects abnormal patterns of head motion associated with defects in initiation of saccades, is also observed in Gaucher's types 2 and 3 . Similar to NP‐C, patterns of abnormal saccades can be used to monitor progression of disease . Gaucher's disease type 1 is the chronic non‐neurological form; however, subtle slowness of saccades has been reported in some patients .…”

Section: Inborn Errors Of Metabolism Associated With Ocular Motor Dismentioning

confidence: 99%

“…30,32 Similar to NP-C, patterns of abnormal saccades can be used to monitor progression of disease. 9,33 Gaucher's disease type 1 is the chronic nonneurological form; however, subtle slowness of saccades has been reported in some patients. 22,[34][35][36] Enzyme replacement therapy and substrate reduction therapy are available.…”

Section: Lysosomal Storage Diseasesmentioning

confidence: 99%

Eye movement disorders and neurological symptoms in late‐onset inborn errors of metabolism

et al. 2018

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Inborn errors of metabolism in adults are still largely unexplored. Despite the fact that adult‐onset phenotypes have been known for many years, little attention is given to these disorders in neurological practice. The adult‐onset presentation differs from childhood‐onset phenotypes, often leading to considerable diagnostic delay. The identification of these patients at the earliest stage of disease is important, given that early treatment may prevent or lessen further brain damage. Neurological and psychiatric symptoms occur more frequently in adult forms. Abnormalities of eye movements are also common and can be the presenting sign. Eye movement disorders can be classified as central or peripheral. Central forms are frequently observed in lysosomal storage disorders, whereas peripheral forms are a key feature of mitochondrial disease. Furthermore, oculogyric crisis is an important feature in disorders affecting dopamine syntheses or transport. Ocular motor disorders are often not reported by the patient, and abnormalities can be easily overlooked in a general examination. In adults with unexplained psychiatric and neurological symptoms, a special focus on examination of eye movements can serve as a relatively simple clinical tool to detect a metabolic disorder. Eye movements can be easily quantified and analyzed with video‐oculography, making them a valuable biomarker for following the natural course of disease or the response to therapies. Here, we review, for the first time, eye movement disorders that can occur in inborn errors of metabolism, with a focus on late‐onset forms. We provide a step‐by‐step overview that will help clinicians to examine and interpret eye movement disorders. © 2018 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

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Saccadic Impairments in Patients with the Norrbottnian Form of Gaucher’s Disease Type 3

Cited by 9 publications

References 16 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

Eye movement biomarkers allow for the definition of phenotypes in Gaucher Disease

Eye movement disorders and neurological symptoms in late‐onset inborn errors of metabolism

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