Successful treatment of cortical visual impairment in children using anti-amblyopia treatment despite the absence of amblyopia: a case report.

BACKGROUND: Cortical visual impairment (CVI) is a verifiable visual dysfunction that cannot be attributed to disorders of the anterior visual pathways or any potentially co-occurring ocular impairment. Given the limited knowledge on the most effective interventions for visual impairment resulting from CVI, this case report provides valuable insights into an example of successful implementation of anti-amblyopia therapy in a patient with CVI. CASE PRESENTATION: This case report presents a 5-year-old girl with CVI secondary to hypoxic-ischemic injury, resulting in visual impairment, dyspraxia, and abnormal visual evoked potential testing. The girl did not suffer from amblyopia, there was no evidence of relevant refractive errors or strabismus, so visual pathway damage was the cause of her visual deficit. Nevertheless, the patient underwent anti-amblyopia therapy and showed significant improvement in visual acuity after 12 months of treatment. The improvement, resulting from visual stimulation, was due to a good functional recovery by a better usage of the damaged visual pathways. The therapy included prescribing corrective glasses and implementing secondary occlusion of the better eye for 4 months, which was protracted for another 4 months, leading to further improvements in visual acuity. CONCLUSIONS: The case report shows that addressing even minor refractive errors and implementing anti-amblyopia therapy can significantly improve vision in children with CVI, even without co-existing amblyopia. It also highlights the importance of early intervention and multidisciplinary rehabilitation in children with CVI, focusing on motor and cognitive skills. Additionally, it emphasizes the need for further research to establish evidence-based practice standards for improving vision in children with CVI.

Patient-advocate-led global coalition adapting fit-for-purpose outcomes measures to assure meaningful inclusion of DEEs in clinical trials.

Existing clinical tools that measure non-seizure outcomes lack the range and granularity needed to capture skills in developmental and epileptic encephalopathy (DEE)-affected individuals who also fall in the severe to profound range of intellectual disability. This effectively excludes those with severe impairments from clinical trials, impeding the ability of sponsors to evaluate disease-modifying therapies (DMTs). The Inchstone Project, an international, patient advocate-led collaboration, brings together leading researchers, clinicians, pharmaceutical companies, and advocates to develop an adapted, validated assessment battery within 5 years. The goal is to support trials of DMTs for the DEEs by providing sufficiently sensitive measurement tools to demonstrate therapeutic efficacy. An initial pilot study administered 7 established assessments to 10 individuals affected by SCN2A-DEE, identifying specific limitations of existing measures and areas for improvement. It was clear that most tools do not account for challenges throughout the DEE population, including vision impairments, significant motor impairments and profound intellectual disability, which need to be accounted for in creating a 'fit-for-purpose' battery for the DEE population. Several novel assessments, including two measures of responsivity developed for use in monitoring recovery after acquired brain injury as well as individualized Goal Attainment Scaling, showed promise in this group. The team also completed a DEE-wide survey with over 270 caregivers documenting their children's abilities and priorities for their improvement from new treatments. The Inchstone team is using this information to evaluate how existing tools might be updated to better capture what is most important to families and measure their child's small but important improvements over time. These efforts are building a coherent picture across multiple DEEs of what domains, or concepts of interest, have the greatest impact on most patients and families. The Inchstone team is on course to adapt non-seizure outcome measures that are (1) sufficiently sensitive to measure small increments of meaningful change ('Inchstones') and (2) applicable to multiple DEE conditions.

DEE-P Connection's Inchstone project is adapting assessment tools to measure the smallest developmental changes in those affected by developmental and epileptic encephalopathies (DEEs) - severe epilepsy and related developmental disorders. More sensitive measures will allow profoundly impacted individuals to be effectively included in clinical trials and result in better DEE treatments. Caregivers of children with DEEs understand firsthand that clinical tools intended to measure non-seizure outcomes, like communication and motor skills, were not designed for and don't work for their children. More sensitive tools are needed to measure the small changes that occur in DEEs. The limitations of existing measurement tools for DEEs have significant consequences: - Non-seizure responses to new therapies cannot be measured without tools designed specifically for individuals with severe to profound intellectual disability.- If a response cannot be measured in a trial, a potentially beneficial impact will be missed and a therapy, having failed to demonstrate an effect, may not gain regulatory approval.- DEE-affected individuals are less likely to benefit from the wave of new disease-modifying therapies providing hope for many other rare genetic diseases. DEE-P Connections, a patient advocacy organization supporting families caring for those severely affected by DEEs, launched The Inchstone Project to address this problem. This team science research collaborative unites researchers, pharmaceutical companies, advocates and others around a shared vision of adapting existing tools to reliably capture the small but important changes in skills in those severely affected by DEEs. To better understand these gaps, the Inchstone team conducted a pilot study with 10 children with SCN2A DEE. The team administered multiple assessments to explore how to adapt the tools to better capture the abilities and growth of this population. The team also completed a comprehensive DEE-wide survey with over 270 caregivers documenting their children's abilities and priorities for their improvement from new treatments, helping to document how existing tools may be updated to better capture what's most important to families and measure their children's small but important improvements over time. The Inchstone Project is on course to assure those profoundly impacted by DEEs are meaningfully included in clinical trials by establishing trusted and reliable non-seizure measurement tools.

Cerebral versus cortical visual impairment: eliminating the conflict and renewing the terminology.

The inconsistency in terminology for Cortical Visual Impairment or Cerebral Visual Impairment presents challenges: (1) different levels of changes in visual pathway and other cerebral areas do not allow discrimination; (2) different visual and oculomotor aspects are not adequately considered. We open a debate to consider a more appropriate diagnosis.

Assessment of Autism Spectrum Disorders in Children with Visual Impairment and Blindness: A Scoping Review.

There is a higher incidence of diagnosed Autism Spectrum Disorder (ASD) in children with visual impairment and blindness (VIB) than in typically sighted children. However, we currently lack appropriate assessment measures to fully understand the neurodevelopment of children with VIB. Numerous factors, such as common characteristics between children with VIB and ASD and the reliance of visual behaviours in assessments of ASD, complicate the clinical and diagnostic understanding of these children. This scoping review aims to describe the published knowledge on ASD assessment in children with VIB. The literature search was performed through MEDLINE, PsycINFO and Scopus. Reference lists of pertinent articles were scrutinized for snowball searching. Articles retained were based on original empirical studies, were relevant to or conducted with children or adolescents with VIB and described assessments for ASD. Pertinent information was extracted, and a thematic analysis was performed. Only 13 articles retrieved pertained to and described the assessment of ASD in children with VIB. The following themes emerged: appropriateness of commonly used ASD assessment tools for children with VIB, modification of pre-existing ASD assessment tools for a better assessment, creation of new assessment tools for this population, time points of assessment, and professional training and practice guidelines. The reviewed literature highlights that there is still much work to be done to better understand the complex relationship between VIB and ASD, and consensus is needed on how best to go about assessing neurodevelopmental disorders in children with VIB.

Aberrant White Matter Development in Cerebral Visual Impairment: A Proposed Mechanism for Visual Dysfunction Following Early Brain Injury.

BACKGROUND: Cerebral visual impairment (CVI) is a common sequala of early brain injury, damage, or malformation and is one of the leading individual causes of visual dysfunction in pediatric populations worldwide. Although patients with CVI are heterogeneous both in terms of underlying etiology and visual behavioural manifestations, there may be underlying similarities in terms of which white matter pathways are potentially altered. This exploratory study used diffusion tractography to examine potential differences in volume, quantitative anisotropy (QA), as well as mean, axial, and radial diffusivities (mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD), respectively) focusing on the dorsal and ventral visual stream pathways in a cohort of young adults with CVI compared to typically sighted and developing controls. METHODS: High angular resolution diffusion imaging (HARDI) data were acquired in a sample of 10 individuals with a diagnosis of CVI (mean age = 17.3 years, 2.97 standard deviation (SD), range 14-22 years) and 17 controls (mean age = 19.82 years, 3.34 SD, range 15-25 years). The inferior longitudinal fasciculus (ILF), inferior fronto-occipital fasciculus (IFOF), vertical occipital fasciculus (VOF), and the three divisions of the superior longitudinal fasciculus (SLF I, II, and III) were virtually reconstructed and average tract volume (adjusted for intracranial volume), MD, AD, and RD were compared between CVI and control groups. As a secondary analysis, an analysis of variance (ANOVA) was carried out to investigate potential differences based on etiology (i.e., CVI due to periventricular leukomalacia (CVI-PVL) and CVI due to other causes (CVI-nonPVL)). RESULTS: We observed a large degree of variation within the CVI group, which minimized the overall group differences in tractography outcomes when examining the CVI sample as a unitary group. In our secondary analysis, we observed significant reductions in tract volume in the CVI-PVL group compared to both controls and individuals with CVI due to other causes. We also observed widespread significant increases in QA, MD, and AD in CVI-PVL compared to the control group, with mixed effects in the CVI-nonPVL group. CONCLUSIONS: These data provide preliminary evidence for aberrant development of key white matter fasciculi implicated in visual perceptual processing skills, which are often impaired to varying degrees in individuals with CVI. The results also indicate that the severity and extent of the white matter changes may be due in part to the underlying cause of the cerebral visual impairments. Additional analyses will need to be done in a larger sample alongside behavioural testing to fully appreciate the relationships between white matter integrity, visual dysfunction, and associated causes in individuals with CVI.

Visual Behaviours (ViBes) in Cerebral Visual Impairment: Validating a Descriptive Tool to Support Diagnosis and Monitoring.

Introduction: Cerebral visual impairment (CVI) is the most common cause of visual impairment in children in the UK. Diagnosis is based on identification of visual behaviours (ViBes) relating to visual dysfunction. Examination techniques and inventories have been developed to elicit these in children with a developmental age of two years or more. The absence of a structured approach to recording visual behaviours in children with complex needs is a barrier to diagnosis. The aim of the study was to develop a matrix of visual behaviours seen in pre-verbal and pre-motor children with visual impairment and establish its content validity and inter-rater reliability. Methods: ViBe content validation:: Visual behaviour descriptors relating to visual function were collated and categorised by expert consensus of vision professionals into a matrix composed of three functions (attention, field/fixation, motor response) and five levels (0 = no awareness; 1 = visual awareness; 2 = visual attention; 3 = visual detection; 4 = visual understanding).ViBe inter-rater reliability:: The participants (two orthoptists, an optometrist, an ophthalmologist and two qualified teachers of the visually impaired) used the ViBe matrix to independently score each of 17 short video clips of children demonstrating visual behaviours seen in CVI. Results: The ViBe matrix will be presented. Cohen's kappa for the matrix was 0.67, demonstrating moderate-to-strong inter-rater reliability. Conclusion: The development of standardised descriptors can support clinicians and teachers in identifying areas of concern for children with complex needs. In addition, the ViBe matrix could be utilised in research, clinical and diagnostic reports to clearly communicate the areas of visual dysfunction and track progress resulting from interventions. Key Points: The absence of a structured approach to recording visual behaviours in children with complex needs is a barrier to diagnosis.The ViBe matrix offers descriptors relating to visual behaviours and has demonstrated acceptable inter-rater reliability.The tool may support the identification and diagnosis of cerebral visual impairment in a population of children who cannot access standard testing.

A Scoping Review of Intervention for Pediatric Cerebral Visual Impairment: Calling All Pediatric Occupational Therapists.

Cerebral visual impairment is the leading cause of low vision in children, and functional gains can be achieved with intervention. To date there exists no evidence-based intervention protocol to guide rehabilitation therapists. This scoping review was conducted to synthesize the evidence currently available and explore current interventions in order to guide future research. This review identified five types of interventions for cerebral visual impairment; habilitation, visual stimulation, video game, color tent, and medical and also evidenced the need for standardized, objective measures of function for this population.

"It's like a guessing game all the time": parent insights on barriers, supports, and priorities for children with cortical visual impairment and complex communication needs.

Parents of children with both cortical visual impairment (CVI) and complex communication needs offer unique perspectives on their children's journeys to receiving proper diagnoses, supports, and interventions, such as augmentative and alternative communication (AAC). This study explored the lived experiences, supports, and barriers identified by parents through a qualitative phenomenological approach. Nine parents of children with both CVI and complex communication needs were interviewed virtually. Results indicated five themes descriptive of the parents' experiences: Challenges Piecing Together a CVI Diagnosis; Dealing with Low Expectations of Others; Parents Empowered to Take Action; Guessing Game to Determine Appropriate AAC to Accommodate CVI; and Aligning Professional Practice with Parent Priorities. Whereas some of these themes echoed the experiences of parents of children with complex communication needs (such as those with cerebral palsy) who were not specifically diagnosed with CVI, other themes were unique to this set of parents including the uncertainty of AAC design and intervention given the challenges of CVI and the necessity of more than one way for children to communicate given their visual challenges. This study highlighted the dire need for continued investigation to determine effective AAC interventions for individuals with CVI.

Research progress on the pathogenesis of CDKL5 pathogenic variants and related encephalopathy.

Cyclin-dependent kinase-like 5 (CDKL5) is a gene encoding a serine/threonine kinase that possesses an N-terminal catalytic domain and a large C-terminal domain and is located on the short arm of the X-chromosome at position 22 (Xp22). CDKL5 regulates neuronal migration, axonal growth, dendritic morphogenesis, and synaptic development and affects synaptic function. Pathogenic variants include deletions, truncations, splice variants, and missense variants. The specificity of CDKL5 is mainly determined by the shared sequence of amino acid residues, which is the phosphorylation site of the target protein with the motif Arg-Pro-X-Ser/Thr-Ala/Pro/Gly/Ser (R-P-X-[S/T]-[A/G/P/S]). Developmental encephalopathy caused by pathogenic variants of CDKL5 has a variety of nervous system symptoms, such as epilepsy, hypotonia, growth retardation, dyskinesia, cortical visual impairment, sleep disorders, and other clinical symptoms. This review summarizes the mechanism of CDKL5-induced allogeneic lesions in the nervous system and the clinical manifestations of related encephalopathy.   Conclusion: This review clarifies CDKL5's participation in neurodevelopmental diseases as well as its crucial function in dividing cells, cultured neurons, knockout mice, and human iPSC-derived neurons. CDKL5 variants help identify clinical diagnostic biomarkers. Although a few direct substrates of CDKL5 have been identified, more must be found in order to fully comprehend the signaling pathways connected to CDKL5 in the brain and the mechanisms that underlie its activities.

Norwegian paediatric habilitation centres judge their own competence on cerebral visual impairment as limited.

AIM: Cerebral visual impairment (CVI), a frequently occurring functional impairment in children with neurodevelopmental disorders, leads to communicative, social and academic challenges. In Norway, children with neurodevelopmental disorders are assessed at paediatric habilitation centres. Our aims were to explore how CVI is identified, how paediatric habilitation centres assess their CVI competence and the reported prevalence of CVI among children with cerebral palsy. METHODS: An electronic questionnaire was sent to all 19 Norwegian paediatric habilitation centre leaders in January 2022. The results were analysed quantitatively and qualitatively. The prevalence of CVI among children with cerebral palsy was estimated using register-based data. RESULTS: The questionnaire was answered by 17. Only three judged their habilitation centre as having sufficient competence on CVI. None of the centres used screening questionnaires systematically, and 11 reported that CVI assessment was not good enough. Awareness that a child may have CVI typically occurred during examinations for other diagnoses. The prevalence of CVI among children with cerebral palsy was only 8%, while CVI status was unknown in 33%. CONCLUSION: Better knowledge and assessment of CVI at Norwegian paediatric habilitation centres are needed. CVI appears to be often overlooked in children with neurodevelopmental disorders.

Evaluation of Behavioral Characteristics in Response to Visual Stimuli in Infants with Cerebral Visual Impairment.

Objectives: To evaluate the behavioral characteristics of infants with cerebral visual impairment (CVI) in response to visual stimuli and the frequency of these features. Materials and Methods: In this retrospective study, 32 infants aged 8-37 months who were referred to the low vision unit in 2019-2021 and diagnosed with CVI based on their demographic characteristics, systemic findings, and standard and functional visual examinations were evaluated. The frequency of ten behavioral characteristics exhibited by infants with CVI in response to visual stimuli as defined by Roman-Lantzy was examined in the patients. Results: The mean age was 23.46±11.45 months, the mean birth weight was 2,550±944 g, and the mean gestational age at birth was 35.39±4.68 weeks. There was hypoxic-ischemic encephalopathy in 22%, prematurity in 59%, periventricular leukomalacia in 16%, cerebral palsy in 25%, epilepsy in 50%, and strabismus in 68.7% of the patients. Color preference for fixation was observed in 40% and visual field preference was observed in 46% of the patients. The most preferred color was red (69%) and the most preferred visual field was right visual field (47%). Difficulty with distance viewing was observed in 84% of patients, visual latency in 72%, need for movement in 69%, absence of visually guided reach in 69%, difficulty with visual complexity in 66%, difficulty with visual novelty in 50%, light-gazing/nonpurposeful gaze in 50%, and atypical visual reflexes in 47%. There was no fixation in 25% of the patients. Conclusion: Behavioral characteristics in response to visual stimuli were observed in most infants with CVI. Knowing and recognizing these characteristic features by ophthalmologists will assist in early diagnosis, referral to visual habilitation, and planning habilitation techniques. These characteristic features are important in order to not miss this critical period in which the brain is still plastic and good responses to visual habilitation can be obtained.

"Even though a lot of kids have it, not a lot of people have knowledge of it": A qualitative study exploring the perspectives of parents of children with cerebral/cortical visual impairment.

BACKGROUND: Cerebral/Cortical Visual Impairment (CVI) is the leading cause of visual impairment in children and can negatively impact participation in daily activities. METHODS AND PROCEDURE: This qualitative study used virtual focus groups and an online questionnaire to understand the perspectives of families with children who have CVI. Constant comparison analysis was used to analyze focus group transcripts and extract themes. The PEDI-CAT and an online questionnaire were administered to characterize the study population. OUTCOMES AND RESULTS: Four themes were identified: (1) Awareness of CVI and its effect on the child and family, (2) Parent experiences, (3) Child factors and functional implications, and (4) Supports that enhance child development/vision. CONCLUSIONS AND IMPLICATIONS: Findings from this study highlight the substantial impact that lack of CVI awareness had on parent experiences. Lack of awareness led to late diagnosis, missed intervention opportunities, and caregiver burden. Due to insufficient resources, parents had to educate themselves and service providers about CVI and advocate for their child's needs. Healthcare and educational providers who work with pediatric neurodevelopmental populations must be knowledgeable about clinical features of CVI, task and environmental adaptations to support vision and implementation of family-centered care.

Deficits in Face Recognition and Consequent Quality-of-Life Factors in Individuals with Cerebral Visual Impairment.

Individuals with cerebral visual impairment (CVI) frequently report challenges with face recognition, and subsequent difficulties with social interactions. However, there is limited empirical evidence supporting poor face recognition in individuals with CVI and the potential impact on social-emotional quality-of-life factors. Moreover, it is unclear whether any difficulties with face recognition represent a broader ventral stream dysfunction. In this web-based study, data from a face recognition task, a glass pattern detection task, and the Strengths and Difficulties Questionnaire (SDQ) were analyzed from 16 participants with CVI and 25 controls. In addition, participants completed a subset of questions from the CVI Inventory to provide a self-report of potential areas of visual perception that participants found challenging. The results demonstrate a significant impairment in the performance of a face recognition task in participants with CVI compared to controls, which was not observed for the glass pattern task. Specifically, we observed a significant increase in threshold, reduction in the proportion correct, and an increase in response time for the faces, but not for the glass pattern task. Participants with CVI also reported a significant increase in sub-scores of the SDQ for emotional problems and internalizing scores after adjusting for the potential confounding effects of age. Finally, individuals with CVI also reported a greater number of difficulties on items from the CVI Inventory, specifically the five questions and those related to face and object recognition. Together, these results indicate that individuals with CVI may demonstrate significant difficulties with face recognition, which may be linked to quality-of-life factors. This evidence suggests that targeted evaluations of face recognition are warranted in all individuals with CVI, regardless of their age.

Longitudinal neurological analysis of moderate and severe pediatric cerebral visual impairment.

Introduction: Cerebral visual impairment (CVI) results from damage to cerebral visual processing structures. It is the most common cause of pediatric visual impairment in developed countries and rising in prevalence in developing nations. There is currently limited understanding on how neurologic, developmental, and ophthalmic factors predict outcome for pediatric CVI. Method: A retrospective manual chart review of pediatric CVI patients seen at the tertiary pediatric hospital neurology and neuro-ophthalmology service between 2010 and 2019 was conducted. Patients were stratified into severity groups (based on a custom CVI grading score), and followed over time to identify outcome predictors. Collected baseline characteristics included perinatal, genetic, developmental, and neurologic history, along with neuroimaging and fundoscopic findings on examination. Longitudinal data collected included age, seizure control, and type of therapy received. Linear mixed-effect models were used for longitudinal CVI grade outcome analysis. Results: A total of 249 individuals spanning 779 patient visits were identified. Mean age at diagnosis was 18.8 ± 16.8 months (2-108 months). About 64.3% were born at term age. Perinatal history revealed hypoxic ischemic encephalopathy (HIE) in 16.5%, intraventricular hemorrhage (IVH) in 11.6%, and seizures in 21.7%. At presentation, 60.3% had a diagnosis of cerebral palsy and 84.7% had developmental delay. Among all subjects, 78.6% had epilepsy; 33.8% had an epileptic encephalopathy, with spasms/hypsarrhythmia being most common. Abnormal neuroimaging was present in 93.8%. Genetic anomalies were present in 26.9%. Baseline visual examination revealed no blink-to-light (BTL) in 24.5%; only BTL in 34.5%, fixation/tracking in 26.5%, and optokinetic drum follow in 14.4%. Longitudinal data analysis showed that perinatal history of HIE, a positive epilepsy history, using multiple (≥3) epilepsy medications, cerebral palsy, and abnormal fundoscopic findings were all negatively associated with CVI grade change over time. After controlling for significant confounders, receiving any type of therapy [early childhood intervention (ECI), physical and occupational therapy (PT/OT), refractive error correction or glasses] was significantly associated with longitudinal improvement in CVI grade compared to patients who did not receive any therapy, with glasses yielding the largest benefit. Conclusion: This study offers extensive insights into neurologic, developmental and ophthalmologic features in patients with moderate to severe CVI. In concordance with previous findings, aspects of perinatal history and epilepsy/seizure control may help inform severity and prognosis in the general neurology or ophthalmology clinic. Conversely, these aspects, as well as genetic and specific epilepsy traits may alert vision health care providers in the clinic to pursue visual evaluation in at-risk individuals. Longitudinal follow-up of CVI patients showed that interventional therapies demonstrated vision function improvement greater than no therapy and maturational development.

The Effectiveness of Sensory Integration Interventions on Motor and Sensory Functions in Infants with Cortical Vision Impairment and Cerebral Palsy: A Single Blind Randomized Controlled Trial.

Cortical vision impairment (CVI) and Cerebral Palsy (CP) lead to decrement in sensory and motor functions of infants. The current study examined the effectiveness of sensory integration interventions on sensory, motor, and oculomotor skills in infants with cortical vision impairment. Thirty-four infants with and CP aged 12−18 months were enrolled to the study. The infants were randomly divided into two groups as the control and intervention groups. The intervention group took sensory integration intervention 2 days a week for 8 weeks in addition to conventional physiotherapy 2 days a week for 8 weeks. The control group only received the conventional physiotherapy program 2 days a week for 8 weeks. The duration of the treatment sessions were 45 min for both interventions. Before and after the intervention, sensory processing functions were evaluated with the Test of Sensory Functions in Infants (TSFI), and motor functions were evaluated with the Alberta Infant Motor Scale (AIMS). There was a statistically significant difference between the pre- and post-test mean TSFI total and AIMS scores in the intervention group and control group (p < 0.001). The intervention group mean TSFI scores were more statistically significant than the those of the control group. Mean post-intervention AIMS scores did not differ between groups. Sensory integration intervention delivered with the conventional physiotherapy program was more effective than the conventional physiotherapy program in increasing sensory processing skills in one measure in infants with CVI and CP.

Homozygosity for a Novel DOCK7 Variant Due to Segmental Uniparental Isodisomy of Chromosome 1 Associated with Early Infantile Epileptic Encephalopathy (EIEE) and Cortical Visual Impairment.

Early infantile epileptic encephalopathy (EIEE) is a severe neurologic and neurodevelopmental disease that manifests in the first year of life. It shows a high degree of genetic heterogeneity, but the genetic origin is only identified in half of the cases. We report the case of a female child initially diagnosed with Leber congenital amaurosis (LCA), an early-onset retinal dystrophy due to photoreceptor cell degeneration in the retina. The first examination at 9 months of age revealed no reaction to light or objects and showed wandering eye movements. Ophthalmological examination did not show any ocular abnormalities. The patient displayed mildly dysmorphic features and a global developmental delay. Brain MRI demonstrated pontine hypo-/dysplasia. The patient developed myoclonic epileptic seizures and epileptic spasms with focal and generalized epileptiform discharges on electroencephalogram (EEG) at the age of 16 months. Genetic screening for a potentially pathogenic DNA sequence variant by whole-exome sequencing (WES) revealed a novel, conserved, homozygous frameshift variant (c.5391delA, p.(Ala1798LeufsTer59)) in exon 42 of the DOCK7 gene (NM_001271999.1). Further analysis by SNP array (Karyomapping) showed loss of heterozygosity (LOH) in four segments of chromosome 1. WES data of the parents and the index patient (trio analysis) demonstrated that chromosome 1 was exclusively inherited from the mother. Four LOH segments of chromosome 1 alternately showed isodisomy (UPiD) and heterodisomy (UPhD). In WES data, the father was a noncarrier, and the mother was heterozygous for this DOCK7 variant. The DOCK7 gene is located in 1p31.3, a region situated in one of the four isodisomic segments of chromosome 1, explaining the homozygosity seen in the affected child. Finally, Sanger sequencing confirmed maternal UPiD for the DOCK7 variant. Homozygous or compound heterozygous pathogenic variants in the DOCK7 (dedicator of cytokinesis 7) gene are associated with autosomal recessive, early infantile epileptic encephalopathy 23 (EIEE23; OMIM #615,859), a rare and heterogeneous group of neurodevelopmental disorders diagnosed during early childhood. To our knowledge, this is the first report of segmental uniparental iso- and heterodisomy of chromosome 1, leading to homozygosity of the DOCK7 frameshift variant in the affected patient.

Working with children with cortical visual impairment who use augmentative and alternative communication: implications for improving current practice.

The aim of this study was to describe how professionals from multiple disciplines (e.g., speech-language pathologists, teachers, occupational therapists) in the United States reported challenges they face in delivering services to children with cortical visual impairment (CVI) who use augmentative and alternative communication (AAC). Three surveys were utilized to identify barriers to and priorities for improving educational and clinical services and in-service and preservice education from the perspectives of professionals in school, community, and university settings. Results suggest that current service delivery models may not be meeting the needs of either children with CVI who use AAC or the professionals whose job it is to provide them with services. Professionals in community-based settings appeared to encounter more barriers. Findings help to support a discussion about approaching AAC interventions for children with CVI who use AAC by adopting interprofessional collaborative practice (IPCP) and interprofessional education (IPE) models, which reflect long-standing best practice guidelines for AAC service delivery and are encouraged by multiple professional organizations.

The clinical approach to the identification of higher-order visual dysfunction in neurodegenerative disease.

PURPOSE OF REVIEW: This review is intended to assist the reader in gaining the knowledge and skills necessary for the recognition and assessment of higher-order visual dysfunction due to neurodegenerative diseases including Alzheimer's disease, dementia with Lewy bodies, Parkinson's dementia, corticobasal degeneration, Creutzfeldt-Jakob disease, and the posterior cortical atrophy syndrome. Clinical problem-solving and pattern recognition must be developed and practiced to accurately diagnosis disturbances of higher-order visual function, and knowledge of higher-order visual brain regions and their visual syndromes forms the foundation for deciphering symptoms presented by patients and/or their care partners. Tests of higher-order visual dysfunction must be assembled by the clinician and assessment can take time and effort. The use of screening tests, follow-up visits, and formal neuropsychological referrals are critical components for accurate diagnosis and these principles are reviewed here. RECENT FINDINGS: A recent survey of neuro-ophthalmologists revealed that over half of the respondents report that 5-10% of their new patient referrals carry a diagnosis of neurodegenerative disease and many patients were referred for visual symptoms of unknown cause. Despite over a century of discovery related to higher-order visual functions of the human brain, translation of discovery to the clinical assessment of patients has been slow or absent. As with the approach to translational medicine in general, to see meaningful progress, an interdisciplinary approach is indispensable. The first step involves the application of discoveries from the field visual neuroscience by clinicians from the fields of ophthalmology, neurology, and neuropsychology, and from the disciplines of neuro-ophthalmology and behavioral neurology. The unmet need for recognition, assessment, and management of higher-order visual dysfunction in neurodegeneration is evident and clinicians can contribute to closing the gap by using the approach and the tools outlined in the review.

Vision Abnormalities in Children and Young Adults With Cerebral Palsy; A Systematic Review.

AIM: The current study was designed to provide detailed information on the prevalence of ocular abnormalities in patients with cerebral palsy (CP). METHODS: Four international online scientific databases, including Web of Science, PubMed, Scopus, and Google Scholar were systemically searched. First, the titles of the articles were evaluated, and if relevant, their abstracts and full texts were reviewed. The quality of the studies was assessed using the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist. RESULTS: A total of 147 articles were found in the initial search. After applying the exclusion criteria, 65 articles were chosen for further review, from which 17 articles, comprising a total of 1734 patients with CP ranging in age from birth to 22 years, passed the STROBE quality check and were included in this review. The prevalence of ocular abnormalities in the CP patients reported in the evaluated studies ranged between 34% to 100%, with refractive error, strabismus, and nystagmus exhibiting the greatest overall prevalence at 52%, 48%, and 11%, respectively in this population. CONCLUSION: Early ocular assessment of children with CP is essential for an accurate diagnosis, personalized rehabilitation and performing early interventions to improve their visual function.