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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.

Neuro-optometric rehabilitation has a broad range of potential rehabilitative applications in neurological and developmental conditions affecting the eye. There is a dearth of evidence supporting its effectiveness, especially in adults. To address this issue, we systematically reviewed literature published in English between January 2000 and June 2022, obtained from search engines such as PubMed, EMBASE, Scopus, and CINAHL, using keywords including “neuro optometry,” “rehabilitation” or a related term, and “oculomotor problem” or “neurological problem” or a related term. Duplicates were eliminated through Mendeley software, and the quality of the selected studies was evaluated using JBI’s critical appraisal tools. Two authors independently reviewed six full-text articles. Relevant data were extracted to Microsoft Excel, and a third author reviewed it. Any uncertainties were resolved through consultation with the last author. Selected studies included adults who had oculomotor problems resulted either from traumatic brain injury/stroke/cerebrovascular accidents and managed with various rehabilitative therapies. Office-based, home-based, or combination therapies with duration ranging from 8 to 12 weeks with the frequency of 2–5 sessions/week were found effective in managing oculomotor problems in adults. However, there is a need for more clinical studies with a larger sample size in this regard.

Neuro-optometric rehabilitation has a broad range of potential rehabilitative applications in neurological and developmental conditions affecting the eye. There is a dearth of evidence supporting its effectiveness, especially in adults. To address this issue, we systematically reviewed literature published in English between January 2000 and June 2022, obtained from search engines such as PubMed, EMBASE, Scopus, and CINAHL, using keywords including "neuro optometry," "rehabilitation" or a related term, and "oculomotor problem" or "neurological problem" or a related term. Duplicates were eliminated through Mendeley software, and the quality of the selected studies was evaluated using JBI's critical appraisal tools. Two authors independently reviewed six full-text articles. Relevant data were extracted to Microsoft Excel, and a third author reviewed it. Any uncertainties were resolved through consultation with the last author. Selected studies included adults who had oculomotor problems resulted either from traumatic brain injury/stroke/cerebrovascular accidents and managed with various rehabilitative therapies. Office-based, home-based, or combination therapies with duration ranging from 8 to 12 weeks with the frequency of 2-5 sessions/week were found effective in managing oculomotor problems in adults. However, there is a need for more clinical studies with a larger sample size in this regard. [ABSTRACT FROM AUTHOR]

Objective: Unusual clinical course. Background: Acquired synkinesis is a well-known phenomenon following oculomotor nerve injury. The abnormal movement appears within the distribution of 1 nerve, or other cranial nerves may be involved. The common misdirection of aberrant regeneration of oculomotor nerve involves the lid, extraocular muscles, or pupil. This report presents a case of aberrant connection between abducens and oculomotor nerve, which is quite rare. Case Report: A 21-year-old man with history of left-sided frontal, lateral orbital wall, and zygomatic fracture from head trauma in a motor vehicle accident presented for evaluation. He was comatose for 6 weeks in the intensive care unit. Six months later, he presented to the ophthalmology clinic for an eye examination. He had no history of eye problems prior to this accident. His best corrected visual acuity in the right eye was 20/20 and the left eye had no light perception. The right eye exam was normal, with normal ocular motility. The left eye exam showed small esotropia in primary position with markedly decreased adduction, elevation, and minimal depression, but on attempted abduction, the left eye would adduct instead. There was no globe retraction when left eye abduction was attempted. The abnormal movement seen resulted from third nerve function during sixth nerve stimulation, due to unusual ocular motility with abnormal connection between the sixth and third cranial nerves. Conclusions: The most likely pathophysiologic mechanism here is peripheral neuronal misdirection hypothesis after trauma. Careful and detailed examination of a patient presenting with unusual ocular motility after trauma is very important. The abnormal connection between the sixth and third cranial nerves is quite rare but can occur. [ABSTRACT FROM AUTHOR]

Abstract Accurate, and objective diagnosis of brain injury remains challenging. This study evaluated useability and reliability of computerized eye-tracker assessments (CEAs) designed to assess oculomotor function, visual attention/processing, and selective attention in recent mild traumatic brain injury (mTBI), persistent post-concussion syndrome (PPCS), and controls. Tests included egocentric localisation, fixation-stability, smooth-pursuit, saccades, Stroop, and the vestibulo-ocular reflex (VOR). Thirty-five healthy adults performed the CEA battery twice to assess useability and test–retest reliability. In separate experiments, CEA data from 55 healthy, 20 mTBI, and 40 PPCS adults were used to train a machine learning model to categorize participants into control, mTBI, or PPCS classes. Intraclass correlation coefficients demonstrated moderate (ICC > .50) to excellent (ICC > .98) reliability (p

Loss-of-function mutations in the X-linked endosomal Na+/H+ exchanger 6 (NHE6) cause Christianson syndrome in males. Christianson syndrome involves endosome dysfunction leading to early cerebellar degeneration, as well as later-onset cortical and subcortical neurodegeneration, potentially including tau deposition as reported in post-mortem studies. In addition, there is reported evidence of modulation of amyloid-β levels in experimental models wherein NHE6 expression was targeted. We have recently shown that loss of NHE6 causes defects in endosome maturation and trafficking underlying lysosome deficiency in primary mouse neurons in vitro. For in vivo studies, rat models may have an advantage over mouse models for the study of neurodegeneration, as rat brain can demonstrate robust deposition of endogenously-expressed amyloid-β and tau in certain pathological states. Mouse models generally do not show the accumulation of insoluble, endogenously-expressed (non-transgenic) tau or amyloid-β. Therefore, to study neurodegeneration in Christianson syndrome and the possibility of amyloid-β and tau pathology, we generated an NHE6-null rat model of Christianson syndrome using CRISPR-Cas9 genome-editing. Here, we present the sequence of pathogenic events in neurodegenerating NHE6-null male rat brains across the lifespan. NHE6-null rats demonstrated an early and rapid loss of Purkinje cells in the cerebellum, as well as a more protracted neurodegenerative course in the cerebrum. In both the cerebellum and cerebrum, lysosome deficiency is an early pathogenic event, preceding autophagic dysfunction. Microglial and astrocyte activation also occur early. In the hippocampus and cortex, lysosome defects precede loss of pyramidal cells. Importantly, we subsequently observed biochemical and in situ evidence of both amyloid-β and tau aggregation in the aged NHE6-null hippocampus and cortex (but not in the cerebellum). Tau deposition is widely distributed, including cortical and subcortical distributions. Interestingly, we observed tau deposition in both neurons and glia, as has been reported in Christianson syndrome post-mortem studies previously. In summary, this experimental model is among very few examples of a genetically modified animal that exhibits neurodegeneration with deposition of endogenously-expressed amyloid-β and tau. This NHE6-null rat will serve as a new robust model for Christianson syndrome. Furthermore, these studies provide evidence for linkages between endolysosome dysfunction and neurodegeneration involving protein aggregations, including amyloid-β and tau. Therefore these studies may provide insight into mechanisms of more common neurodegenerative disorders, including Alzheimer's disease and related dementias.

IntroductionClinical diagnosis of Parkinsonism is still challenging, and the diagnostic biomarkers of Multiple System Atrophy (MSA) are scarce. This study aimed to investigate the diagnostic value of the combined eye movement tests in patients with Parkinson's disease (PD) and those with MSA.MethodsWe enrolled 96 PD patients, 33 MSA patients (18 with MSA-P and 15 with MSA-C), and 40 healthy controls who had their horizontal ocular movements measured. The multiple-step pattern of memory-guided saccade (MGS), the hypometria/hypermetria of the reflexive saccade, the abnormal saccade in smooth pursuit movement (SPM), gaze-evoked nystagmus, and square-wave jerks in gaze-holding test were qualitatively analyzed. The reflexive saccadic parameters and gain of SPM were also quantitatively analyzed.ResultsThe MGS test showed that patients with either diagnosis had a significantly higher incidence of multiple-step pattern compared with controls (68.6%, 65.2%, and versus. 2.5%, p

Globular glial tauopathy (GGT) is a rare 4-repeat tauopathy characterized by the accumulation of tau globular inclusions in astrocytes and oligodendrocytes. Several clinical phenotypes have been associated with GGT, making the prediction of this rare pathological entity difficult. We report the case of a patient with eye-movement abnormalities and gait instability, reminiscent of progressive supranuclear palsy-Richardson's syndrome (PSP-RS), who later developed upper motor neuron symptoms suggestive of primary lateral sclerosis (PLS). Neuropathological assessment revealed GGT type III pathology. A theoretical framework is proposed to help clinicians predict GGT in subjects with coexistent features of PSP-RS and PLS.

PURPOSE: To study effects of age and horizontal duction on deformation of the optic nerve head (ONH) and peripapillary retina (PPR), as reflected by displacement of vascular landmarks, to explore the influence of adduction tethering. DESIGN: Cross-sectional study. METHODS: Setting: University. STUDY POPULATION: Single eyes of 20 healthy young adults (average age 23.9 ± 3.9 [SD] years) were compared to 20 older subjects (average age 61.4 ± 9.3 years). Observational Procedure: The disc and PPR were imaged by scanning laser ophthalmoscopy in central gaze and at 35 degrees abduction and adduction. MAIN OUTCOME MEASURE: Deformations of the disc and adjacent PPR were measured by comparing positions of epipapillary and epiretinal blood vessels. RESULTS: Vessels within the ONH of younger subjects shifted temporally during adduction and nasally during abduction. Displacement of the nasal hemi-disc in adduction was greater at 38.5 ± 1.7 μm (standard error of mean) than the temporal half at 4.1 ± 2.1 μm (P < .001). PPR within 1 radius of the disc margin underwent 7.6 ± 1.6 μm average temporal displacement in adduction in young subjects. In abduction, the young temporal hemi-disc shifted 4.4 ± 0.6 μm nasally without significant displacement in the nasal half. Older subjects ONH showed less temporal shift and less displacement in the PPR within 1 disc radius (P < .0001) in adduction; the nasal hemi-disc shifted 24.5 ± 1.3 μm compared with 4.4 ± 2.1 μm in the temporal half. There were no significant deformations of the disc during abduction by older subjects. CONCLUSION: Large horizontal duction, particularly adduction, deforms the disc and peripapillary vasculature. This deformation, which is larger in younger than older subjects, may be due to optic nerve tethering in adduction.

Posterior circulation stroke can present with dizziness/vertigo without other general neurological symptoms or signs, making it difficult to detect, and missed stroke can deteriorate. Therefore, a sign that can be easily identified during an examination would be helpful to improve the detection of this type of stroke. The objective of this review is to highlight an ocular sign that is seen in posterior circulation strokes called ocular lateral deviation (OLD). OLD is mostly seen in dorsolateral medullary strokes, and it is also seen in pontine and cerebellar strokes. OLD is detected by asking a patient to look straight ahead and then briefly close their eyes. Upon re-opening their eyes, the examiner will see that the eyes have deviated to one side; the patient's eyes will then make corrective saccade(s) to return to looking straight ahead. Complete eye deviation is a central sign of posterior circulation stroke. OLD is an under-recognized vestibular ocular sign of central vestibulopathies including posterior circulation stroke. The most common location is in the dorsolateral medulla, where one-third of such strokes have complete OLD. Eye deviation can also be appreciated on computed tomography or magnetic resonance imaging. OLD can be detected up to 6 months after a posterior circulation stroke. Checking for the sign of complete eye deviation in patients with dizziness/vertigo could be a simple, quick method for detecting posterior circulation stroke, and a means to improving the patients' outcome. [ABSTRACT FROM AUTHOR]

Purpose: To describe clinical manifestations and short-term prognosis of ocular motility disorders following coronavirus disease-2019 (COVID-19) vaccination. Methods: Ocular motility disorders were diagnosed by clinical assessment, high-resolution magnetic resonance imaging, and laboratory testing. Clinical manifestations, short-term prognosis, and rate of complete recovery were analyzed. Results: Sixty-three patients (37 males, 26 females) with a mean age of 61.6 ± 13.3 years (range, 22–81 years) were included in this study. Among 61 applicable patients with sufficient information regarding medical histories, 38 (62.3%) had one or more significant underlying past medical histories including vasculopathic risk factors. The interval between initial symptoms and vaccination was 8.6 ± 8.2 (range, 0–28) days. Forty-two (66.7%), 14 (22.2%), and 7 (11.1%) patients developed symptoms after the first, second, and third vaccinations, respectively. One case of internuclear ophthalmoplegia, 52 cases of cranial nerve palsy, two cases of myasthenia gravis, six cases of orbital diseases (such as myositis, thyroid eye disease, and IgG-related orbital myopathy), and two cases of comitant vertical strabismus with acute onset diplopia were found. Among 42 patients with follow-up data (duration: 62.1 ± 40.3 days), complete improvement, partial improvement, no improvement, and exacerbation were shown in 20, 15, 3, and 4 patients, respectively. Conclusion: This study provided various clinical features of ocular motility disorders following COVID-19 vaccination. The majority of cases had a mild clinical course while some cases showed a progressive nature. Close follow-up and further studies are needed to elucidate the underlying mechanisms and long-term prognosis. [ABSTRACT FROM AUTHOR]

BackgroundThe Movement Disorder Society criteria for progressive supranuclear palsy define diagnostic allocations, stratified by certainty levels and clinical predominance types. We aimed to study the frequency of ambiguous multiple allocations and to develop rules to eliminate them.MethodsWe retrospectively collected standardized clinical data by chart review in a multicenter cohort of autopsy-confirmed patients with progressive supranuclear palsy, to classify them by diagnostic certainty level and predominance type and to identify multiple allocations.ResultsComprehensive data were available from 195 patients. More than one diagnostic allocation occurred in 157 patients (80.5%). On average, 5.4 allocations were possible per patient. We developed four rules for Multiple Allocations eXtinction (MAX). They reduced the number of patients with multiple allocations to 22 (11.3%), and the allocations per patient to 1.1.ConclusionsThe proposed MAX rules help to standardize the application of the Movement Disorder Society criteria for progressive supranuclear palsy. © 2019 International Parkinson and Movement Disorder Society.

Objective: To identify eye conditions associated to social distancing and related increase in screen time exposure on children and teenagers. Methods: Observational, descriptive and analytical study, with a cross-section design, carried out between July and August 2021, by questionnaire survey. Results: Headaches related to excessive screen time exposure were reported by 26.51% of the students surveyed, while 38.8% reported suspect convergence insufficiency. Regarding the questionnaire about dry eye, 18.8% were symptomatic and 7.5% reported hard-to-manage symptoms. Computers were the devices most used for schoolwork (71.5%), followed by cellphones on second place (66.3%). Symptomatic cases of dry eye were mostly reported by participants that did not make use of computers (36.4%). It was not possible to establish a connection between convergence insufficiency and device usage time. Those participants that reported more screen time exposure also reported an increased percentage of hard-to-manage symptoms (42.9%), regarding dry eye. Conclusion: Dry eye and convergence insufficiency symptoms were more prevalent in the surveyed population. [ABSTRACT FROM AUTHOR]

Purpose The aim of this study was to review the available scientific literature on the possible relationship between the visual system and motor development in children. Methods: This study was performed according to the Preferred Reporting Items for Systematic Reviews (PRISMA) statement recommendations. The review protocol is available in PROSPERO (CRD42021245341). Four different databases, namely Scopus, PubMed, CINAHL and Web of Science, were assessed from April 2005 to February 2021. To determine the quality of the articles, we used the Critical Appraisal Skills Programme (CASP) Quality Appraisal Scale, and a protocol was followed to define the levels of evidence on the basis of the Centre for Evidence‐Based Medicine Levels of Evidence. The search strategy included terms describing motor development in children and adolescents with visual disorders. Results: Among the identified studies, 23 were included in the study. All selected articles examined the relationship between the visual system and development in children. The quality of most of the studies was moderate–high, and they were between evidence levels 2 and 4. Conclusions: Our systematic review revealed that all included studies established a relationship between the visual system and development in children. However, the methods for measuring the visual system and motor skills lacked uniformity. [ABSTRACT FROM AUTHOR]