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.
- MeSH
- biologické markery MeSH
- konsensus * MeSH
- lidé MeSH
- pohyby očí fyziologie MeSH
- poruchy hybnosti oka diagnóza patofyziologie genetika MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- systematický přehled MeSH
Characterizing bedside oculomotor deficits is a critical factor in defining the clinical presentation of hereditary ataxias. Quantitative assessments are increasingly available and have significant advantages, including comparability over time, reduced examiner dependency, and sensitivity to subtle changes. To delineate the potential of quantitative oculomotor assessments as digital-motor outcome measures for clinical trials in ataxia, we searched MEDLINE for articles reporting on quantitative eye movement recordings in genetically confirmed or suspected hereditary ataxias, asking which paradigms are most promising for capturing disease progression and treatment response. Eighty-nine manuscripts identified reported on 1541 patients, including spinocerebellar ataxias (SCA2, n = 421), SCA3 (n = 268), SCA6 (n = 117), other SCAs (n = 97), Friedreich ataxia (FRDA, n = 178), Niemann-Pick disease type C (NPC, n = 57), and ataxia-telangiectasia (n = 85) as largest cohorts. Whereas most studies reported discriminatory power of oculomotor assessments in diagnostics, few explored their value for monitoring genotype-specific disease progression (n = 2; SCA2) or treatment response (n = 8; SCA2, FRDA, NPC, ataxia-telangiectasia, episodic-ataxia 4). Oculomotor parameters correlated with disease severity measures including clinical scores (n = 18 studies (SARA: n = 9)), chronological measures (e.g., age, disease duration, time-to-symptom onset; n = 17), genetic stratification (n = 9), and imaging measures of atrophy (n = 5). Recurrent correlations across many ataxias (SCA2/3/17, FRDA, NPC) suggest saccadic eye movements as potentially generic quantitative oculomotor outcome. Recommendation of other paradigms was limited by the scarcity of cross-validating correlations, except saccadic intrusions (FRDA), pursuit eye movements (SCA17), and quantitative head-impulse testing (SCA3/6). This work aids in understanding the current knowledge of quantitative oculomotor parameters in hereditary ataxias, and identifies gaps for validation as potential trial outcome measures in specific ataxia genotypes.
- MeSH
- ataxie MeSH
- Friedreichova ataxie * MeSH
- genotyp MeSH
- lidé MeSH
- pohyby očí MeSH
- progrese nemoci MeSH
- spinocerebelární degenerace * MeSH
- teleangiektatická ataxie * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) je autozomálně recesivní neurodegenerativní onemocnění z okruhu hereditárních ataxií s pozdním začátkem postihující mozeček, senzitivní nervy a vestibulární systém. Jeho genetická příčina byla odhalena v roce 2019 a od roku 2020 je dostupné také diagnostické molekulárně genetické vyšetření. Dle dosavadní literatury se ukazuje, že CANVAS je nejčastější příčinou hereditární ataxie s pozdním nástupem. Ve skupině prvních devíti vyšetřených pacientů s podezřením na toto onemocnění jsme zachytili čtyři případy CANVAS, tři pacienty podrobně popisujeme v této práci.
Cerebellar ataxia, neuropathy, vestibular areflexia syndrome (CANVAS) is an autosomal recessive neurodegenerative disease from hereditary ataxias with a late onset that affects the cerebellum, sensory nerves, and the vestibular system. Its genetic cause was discovered in 2019 and since 2020, diagnostic molecular genetic testing has also been available. According to the existing literature, it seems that CANVAS is a major cause of late onset hereditary ataxia. Out of the first nine examined patients with the suspected disease, we confirmed four cases of CANVAS; three of the patients are described in detail in this manuscript.
- Klíčová slova
- CANVAS,
- MeSH
- cerebelární ataxie * diagnóza MeSH
- lidé MeSH
- neuralgie * MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- spinocerebelární degenerace diagnóza MeSH
- vestibulární neuronitida MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
Deterioration of dynamic visual acuity (DVA) as a result of impaired vestibulo-ocular reflex (VOR) has been well described in peripheral vestibulopathies, however, changes in DVA in patients with degenerative cerebellar ataxias (CA) and its relation to VOR impairment in these patients has not yet been evaluated. Our aim was to assess the alterations of DVA in CA and to evaluate its relation to vestibular function. 32 patients with CA and 3 control groups: 13 patients with unilateral and 13 with bilateral vestibulopathy and 21 age matched healthy volunteers were examined by clinical DVA test, VOR was assessed by video Head Impulse Test and caloric irrigation. The severity of ataxia in CA was assessed by Scale for the assessment and rating of ataxia (SARA). Relationship between DVA and vestibular function in CA patients was examined by linear regressions. DVA impairment was highly prevalent in CA patients (84%) and its severity did not differ between CA and bilateral vestibulopathy patients. The severity of DVA impairment in CA was linked mainly to VOR impairment and only marginally to the degree of ataxia. However, DVA impairment was present also in CA patients without significant vestibular lesion showing that central mechanisms such as impairment of central adaptation of VOR are involved. We suggest that the evaluation of DVA should be a standard part of clinical evaluation in patients with progressive CA, as this information can help to target vestibular and oculomotor rehabilitation.
- MeSH
- cerebelární ataxie * MeSH
- lidé MeSH
- pulsní rotační test MeSH
- vestibulární nemoci * MeSH
- vestibulookulární reflex MeSH
- zraková ostrost MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Klíčová slova
- Rombergovy zkoušky, polohové manévry,
- MeSH
- fyziologický nystagmus MeSH
- lidé MeSH
- neurologické vyšetření * klasifikace MeSH
- patologický nystagmus diagnóza etiologie MeSH
- pohyby očí MeSH
- pulsní rotační test MeSH
- sakadické oční pohyby MeSH
- vertigo * diagnóza MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
OBJECTIVES: This study aimed to assess vestibular function in 39 patients who underwent neurectomy for vestibular schwannoma. METHOD: Semicircular canal reactivity was measured by video head-impulse test using high-frequency passive head acceleration. Response gain was calculated as a ratio between the areas under the eye-velocity curve and the head-velocity curve. STATISTICAL ANALYSIS: Student t-test was used for to compare quantitative variables. ANOVA was used to test inter-group differences in categoric variables. RESULTS: In all cases, surgery-side gain on head impulse test was low, with increased gain asymmetry. A subgroup of 7 patients (18%) showed relatively high gain in vestibulo-ocular reflex on the surgery side. Caloric reaction was absent in all cases. These findings indicate that residual vestibular function can be conserved following vestibular schwannoma extirpation. CONCLUSION: Cases with moderate vestibulo-ocular reflex gain were a subgroup with partial conservation of vestibular nerve fibers. Whether this is a predictor of better functional prognosis remains to be elucidated. Higher gain correlated with less extensive surgery and sparing of the inferior vestibular nerve. Low gain correlated with complete vestibular neurectomy. This information may guide rehabilitation strategy following surgery.
- MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- nervová vlákna MeSH
- neurochirurgické výkony metody MeSH
- pooperační komplikace patofyziologie MeSH
- pooperační období MeSH
- prognóza MeSH
- pulsní rotační test MeSH
- senioři MeSH
- vestibulární aparát patofyziologie MeSH
- vestibulární funkční testy MeSH
- vestibulární schwannom patofyziologie chirurgie MeSH
- vestibulookulární reflex MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: 3 Hz postural tremor was described in patients with anterior cerebellar lobe atrophy, however sensitivity and specificity of this sign in degenerative cerebellar diseases has not yet been evaluated. Our aim was to assess the 3 Hz tremor in patients with cerebellar ataxia, compare its sensitivity and specificity with other posturography parameters and to find out a correlation of intensity of 3 Hz tremor with ataxia severity. METHODS: 30 patients with degenerative cerebellar ataxia, a control group of 30 patients with compensated peripheral vestibulopathy and 40 healthy volunteers were examined by posturography. 3 Hz tremor was assessed both qualitatively and quantitatively, its sensitivity and specificity were compared with other standard posturography parameters. RESULTS: 3 Hz postural tremor was detected in 90% of patients with cerebellar ataxia, with 100% specificity and 90% sensitivity. The sensitivity and specificity of quantitative analysis of 3 Hz tremor was largely superior to standard posturography parameters when differentiating patients with cerebellar ataxia from vestibular impairment and healthy controls. CONCLUSION: 3 Hz postural tremor is highly sensitive and specific sign of cerebellar impairment in patients with cerebellar ataxia. SIGNIFICANCE: Evaluation of 3 Hz postural tremor should be a standard part of posturography examination when considering a cerebellar impairment.
- MeSH
- atrofie patofyziologie MeSH
- cerebelární ataxie etiologie patofyziologie MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mozeček patofyziologie MeSH
- postura těla fyziologie MeSH
- posturální rovnováha fyziologie MeSH
- senzitivita a specificita MeSH
- tremor patofyziologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Výraz „ataxie“ se používá jak ve významu porušeného, nepravidelného pohybu, tak jako označení skupiny dědičných chorob. Ta se denně rozrůstá o nové genetické objevy a dochází ke zpřesňování jejich feno-/genotypové korelace. V souvislosti s rozvojem vyšetřovacích zobrazovacích a elektrofyziologických metod se však dostává do pozadí klinická typizace ataxie jako symptomu, který může být neurologovi dobrým vodítkem v diferenciálně-diagnostické rozvaze o etiologii obtíží pacienta. Následující text je proto věnován pohledu na ataxii jako na syndrom, jsou probrána specifika ataxie z hlediska jejího zařazení a v závěru jsou stručně nastíněny nejčastější či záludné příčiny, které mohou ataxii způsobovat, event. imitovat.
Term “ataxia” means impaired, irregular movement, but is also known as a group of hereditary diseases. Thanks to progress in molecular genetics, new types of ataxia are found daily, together with specification of phenotype-genotype correlation. With progress in neuroimaging and electrophysiology, ataxia as a symptom might not get the appropriate attention of clinicians. However, clinical features of ataxia can serve as an important clue in differential diagnosis. This text describes ataxia as a syndrome. We discussed specific signs of ataxia from a syndromological point of view and highlighted the most common causes of ataxia and some of the rare causes imitating ataxia as well.
- Klíčová slova
- senzitivní ataxie, vestibulární ataxie,
- MeSH
- akutní nemoc MeSH
- ataxie chůze diagnóza etiologie patofyziologie MeSH
- ataxie diagnóza etiologie patofyziologie MeSH
- cerebelární ataxie diagnóza etiologie patofyziologie MeSH
- chronická nemoc MeSH
- diferenciální diagnóza MeSH
- lidé MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
