Abnormal Eye Movements Research Articles

SRPK3 Is Essential for Cognitive and Ocular Development in Humans and Zebrafish, Explaining X-Linked Intellectual Disability.

Intellectual disability is often the outcome of neurodevelopmental disorders and is characterized by significant impairments in intellectual and adaptive functioning. X-linked intellectual disability (XLID) is a subset of these disorders caused by genetic defects on the X chromosome, affecting about 2 out of 1,000 males. In syndromic form, it leads to a broad range of cognitive, behavioral, ocular, and physical disabilities. Employing exome or genome sequencing, here we identified 4 missense variants (c.475C > G; p.H159D, c.1373C > A; p.T458N, and c.1585G > A; p.E529K, c.953C > T; p.S318L) and a putative truncating variant (c.1413_1414del; p.Y471*) in the SRPK3 gene in 9 XLID patients from 5 unrelated families. To validate SRPK3 as a novel XLID gene, we established a knockout (KO) model of the SRPK3 orthologue in zebrafish. The 8 patients ascertained postnatally shared common clinical features including intellectual disability, agenesis of the corpus callosum, abnormal eye movement, and ataxia. A ninth case, ascertained prenatally, had a complex structural brain phenotype. Together, these data indicate a pathological role of SRPK3 in neurodevelopmental disorders. In post-fertilization day 5 larvae (free swimming stage), KO zebrafish exhibited severe deficits in eye movement and swim bladder inflation, mimicking uncontrolled ocular movement and physical clumsiness observed in human patients. In adult KO zebrafish, cerebellar agenesis and behavioral abnormalities were observed, recapitulating human phenotypes of cerebellar atrophy and intellectual disability. Overall, these results suggest a crucial role of SRPK3 in the pathogenesis of syndromic X-linked intellectual disability and provide new insights into brain development, cognitive and ocular dysfunction in both humans and zebrafish. ANN NEUROL 2024;96:914-931.

Ocular and systemic manifestations of Joubert syndrome: A case report

Joubert syndrome (JS) is a group of rare disorders that stem from defects in sensory organelle, the primary cilia. Affected patients often present with disorders affecting multiple systems, including the brain, eye, and kidneys. Oculomotor apraxia is the most frequent ocular manifestation (80%), followed by strabismus (74%) and nystagmus (72%). A minority of patients also present with ptosis (43%), chorioretinal coloboma (30%), and optic nerve atrophy (22%). Common symptoms include breathing abnormalities, mental developmental delays, loss of voluntary muscle coordination, and abnormal eye movements, with diagnostic “molar tooth” sign observed by magnetic resonance imaging of the midbrain. Hepatic and renal function need to be monitored. Delayed diagnosis is usually related to its variable, nonspecific presentation. Awareness of the characteristic clinical and radiological findings in JS will help in early diagnosis, appropriate counseling, and proper rehabilitation.

A case of alternating hemiplegia in 2-month-old children with nystagmus as the first symptom: A case report.

This case report delves into the rare neurological condition known as alternating hemiplegia of childhood (AHC), focusing on its clinical manifestations, diagnostic approaches, and treatment options. AHC typically presents in infants under the age of 18 months with intermittent episodes of hemiplegia, often triggered by stressors such as environmental changes, bathing, or emotional stress. Recognizing the clinical features of AHC is crucial for early identification and intervention. The paper presents a case of a 2-month-old child with nystagmus as the initial symptom, followed by limb movement disorder in the left upper limb and weakness in the right limbs. The child's condition did not improve with treatment at an external hospital, highlighting the complexity of the disease and the need for specialized care. After a comprehensive review of the patient's medical history, physical examination, and imaging studies, the child was diagnosed with AHC. The diagnosis was confirmed through video electroencephalogram and whole-exome gene detection, which revealed a de novo mutation in the ATP1A3 gene, identified as pathogenic according to the American College of Medical Genetics and Genomics guidelines. The child was admitted to Peking University First Hospital and treated with levetiracetam and flunarizine oral administration. These medications were chosen for their efficacy in managing the symptoms of AHC, particularly the hemiplegic episodes. Post-treatment, the child experienced a reduction in the frequency and intensity of hemiplegic attacks compared to the initial stage. However, the child still exhibited paroxysmal symptoms and abnormal eye movements, and developmental milestones were delayed, indicating the need for ongoing care and monitoring. This case underscores the importance of early recognition and prompt intervention in managing children with AHC. The varied clinical presentations of AHC necessitate vigilance for early differential diagnosis. Although AHC is currently incurable, appropriate treatment can mitigate the impact of complications and improve the long-term quality of life for affected children, facilitating better societal integration.

Study of Eye Movements Abnormalities in Epilepsy

ABSTRACT Idiopathic epilepsy (IE), is a group of epileptic syndromes with no structural brain lesion, but with microstructural changes in neuronal networks leading to neuropsychological consequences. Therefore, the assessment of saccadic eye movements can provide insight into the integrity of cerebral networks as it involves large cortical and subcortical brain areas and circuitries. Describe saccadic eye movement abnormalities in patients with IE and correlate them with disease characteristics and antiseizure medication. Case–control study including IE patients followed in the Neurology Department of Razi University Hospital and healthy controls matched. Participants underwent a recording of saccadic eye movements. Pursuit, prosaccade, and anti-saccade tasks were performed. 115 patients and 98 matched healthy controls were included. The gender ratio (male to female) was 0.6. The mean age at onset was 16.3 ± 12 years. Diagnosed epileptic syndromes were juvenile myoclonic epilepsy (JME), epilepsy with generalized tonic-clonic seizures, childhood absence epilepsy, temporal lobe epilepsy, frontal lobe epilepsy, and rolandic epilepsy. Saccadic eye movements were impaired in 52.2% of our patients and significantly more altered in those with JME (p = .021). Prolonged horizontal saccades latencies were the most frequent eye movement abnormalities (32.1%), followed by altered horizontal smooth pursuit (22.6%). A positive correlation was found between age at eye movements recording, age at onset, disease duration, global cognitive impairment, and saccadic eye movements. However, no definite relationship was identified. Saccadic eye movement illustrates extending anatomic alterations in IE including frontal and temporoparietal cortical areas and cortico-subcortical circuits. Eye movement recording is a useful and reproducible tool in the assessment of epileptic patients and provides a better understanding of neuronal mechanisms in epilepsy.

Fine spatial vision is optimally adapted to the abnormal fixational eye movements of people with amblyopia

Fine spatial vision is optimally adapted to the abnormal fixational eye movements of people with amblyopia

A Novel MAG Variant Causes Hereditary Spastic Paraplegia in a Consanguineous Pakistani Family.

Background and objectives: Hereditary spastic paraplegia (HSP) is characterized by unsteady gait, motor incoordination, speech impairment, abnormal eye movement, progressive spasticity and lower limb weakness. Spastic paraplegia 75 (SPG75) results from a mutation in the gene that encodes myelin associated glycoprotein (MAG). Only a limited number of MAG variants associated with SPG75 in families of European, Middle Eastern, North African, Turkish and Palestinian ancestry have been documented so far. This study aims to provide further insight into the clinical and molecular manifestations of HSP. Methods: Using whole-exome sequencing, we investigated a consanguineous Pakistani family where three individuals presented with clinical signs of HSP. Sanger sequencing was used to carry out segregation analysis on available family members, and a minigene splicing assay was utilized to evaluate the effect of the splicing variant. Results: We identified a novel homozygous pathogenic splice donor variant in MAG (c.46 + 1G > T) associated with SPG75. RNA analysis revealed exon skipping that resulted in the loss of a start codon for ENST00000361922.8 isoform. Affected individuals exhibited variable combinations of nystagmus, developmental delay, cognitive impairments, spasticity, dysarthria, delayed gait and ataxia. The proband displayed a quadrupedal stride, and his siblings experienced frequent falls and ataxic gait as one of the prominent features that have not been previously reported in SPG75. Conclusions: Thus, the present study presents an uncommon manifestation of SPG75, the first from the Pakistani population, and broadens the spectrum of MAG variants.

Joubert syndrome: a rare cause of hypotonia with developmental delay

Joubert syndrome is a rare autosomal recessive disorder. It is characterized by congenital ataxia, hypotonia, developmental delay, and at least one of the following features: neonatal respiratory disturbances and abnormal eye movements; including nystagmus and oculomotor apraxia. Molar tooth appearance is an essential finding for the diagnosis of Joubert syndrome. Here we presented a case of an 18-month-old male who presented with developmental delay and marked hypotonia. The main purposes of the case report were to highlight the benefit of a multidisciplinary rehabilitation team approach and describe the clinical features associated with Joubert syndrome. Brain magnetic resonance imaging showed a thick, elongated, and abnormally oriented superior cerebellar peduncle showing a molar tooth appearance with elongated bat-wing-shaped 4th ventricle and hypoplasia of the vermis suggestive of JS. Hypotonia during infancy and developmental delay with or without learning disability, associated with abnormal breathing patterns and abnormal eye movements (nystagmus) along with the radiological presence of a molar tooth sign on the brain MRI is an essential component to confirm the diagnosis.

Intralesional epileptiform activity in a fourth ventricular hamartoma associated with epileptic hemifacial spasm in a toddler: illustrative case.

Focal epilepsy caused by a posterior fossa lesion is a rare phenomenon. In these cases, seizure onset typically occurs during the first few months of life, with episodes of epileptic hemifacial spasms and abnormal eye movements. Patients often present with drug-resistant epilepsy and often require resection for the best chance of seizure freedom. The authors present the case of a 19-month-old male with intractable epileptic hemifacial spasms and a dorsally exophytic right brainstem and middle cerebellar peduncle hamartoma, following 2 prior subtotal resections. The authors recommended a third suboccipital craniotomy with intraoperative electrocorticography, which revealed interictal spiking from an intralesional depth electrode. Near-total resection led to durable seizure freedom. Although posterior fossa lesions are rarely associated with epileptiform activity, this case demonstrates that pediatric patients with epileptic hemifacial spasms associated with a posterior fossa lesion may respond favorably to resection. Furthermore, this case demonstrates that intralesional electrocorticography can detect epileptic activity in posterior fossa lesions, which may predict postoperative seizure outcomes. https://thejns.org/doi/10.3171/CASE2452.

Spinocerebellar ataxia type 4 is caused by a GGC expansion in the ZFHX3 gene and is associated with prominent dysautonomia and motor neuron signs.

Spinocerebellar ataxia 4 (SCA4), characterized in 1996, features adult-onset ataxia, polyneuropathy, and linkage to chromosome 16q22.1; its underlying mutation has remained elusive. To explore the radiological and neuropathological abnormalities in the entire neuroaxis in SCA4 and search for its mutation. Three Swedish families with undiagnosed ataxia went through clinical, neurophysiological, and neuroimaging tests, including PET studies and genetic investigations. In four cases, neuropathological assessments of the neuroaxis were performed. Genetic testing included short read whole genome sequencing, short tandem repeat analysis with ExpansionHunter de novo, and long read sequencing. Novel features for SCA4 include dysautonomia, motor neuron affection, and abnormal eye movements. We found evidence of anticipation; neuroimaging demonstrated atrophy in the cerebellum, brainstem, and spinal cord. [18F]FDG-PET demonstrated brain hypometabolism and [11C]Flumazenil-PET reduced binding in several brain lobes, insula, thalamus, hypothalamus, and cerebellum. Moderate to severe loss of Purkinje cells in the cerebellum and of motor neurons in the anterior horns of the spinal cord along with pronounced degeneration of posterior tracts was also found. Intranuclear, mainly neuronal, inclusions positive for p62 and ubiquitin were sparse but widespread in the CNS. This finding prompted assessment for nucleotide expansions. A polyglycine stretch encoding GGC expansions in the last exon of the zink finger homeobox 3 gene was identified segregating with disease and not found in 1000 controls. SCA4 is a neurodegenerative disease caused by a novel GGC expansion in the coding region of ZFHX3, and its spectrum is expanded to include dysautonomia and neuromuscular manifestations.

Changes in saccadic intrusions over time as an objective biomarker to follow ALS disease progression

Objective: Saccadic Intrusions (SIs) are abnormal eye movements during gaze fixation. Studies have indicated the clinical relevance of SIs, especially of square wave jerks (SWJ) in ALS. We used a software-based platform to extract SIs as a part of an interventional drug trial. The objective was to examine SIs’ change over time as a potential biomarker of ALS disease progression. Methods: 28 ALS patients (61.95 ± 8.6 years) were assessed with the revised ALS Functional Rating Scale (ALSFRS-R) and with an oculometric test. Changes of SIs over time and correlations with ALSFRS-R and its bulbar subscale were calculated. A power calculation was conducted to understand the practical implications of results. Results: A significant increase of SWJ over trial duration was observed, with an increase in frequency (mean rise of 0.14 ± 0.28, p < 0.01), amplitude (0.001 ± 0.0016 degrees, p < 0.005), overall duration of SWJ (0.13 ± 0.25, in %, p < 0.01), and in their relative part out of all intrusions (0.18 ± 0.32, in %, p < 0.005). Negative correlations were found with the bulbar subscale (R=-0.43, −0.41, −0.39 and −0.47, respectively, p < 0.001). The required sample size for observing a 40% reduction in bulbar aspects when using the oculometric test (α = 0.05 and β = 0.8), was found to be 150 patients per arm, compared with 200 patients using the bulbar subscale. Conclusions: Evaluation of saccadic intrusions during fixation was able to detect disease progression over time, correlated with ALSFRS-R bulbar subscale. Eye movements can potentially serve as an objective biomarker in ALS clinical trials and reduce the required sample size to show clinical effect of therapies.

Consequences of eye movements for spatial selectivity

What determines spatial tuning in the visual system? Standard views rely on the assumption that spatial information is directly inherited from the relative position of photoreceptors and shaped by neuronal connectivity.1,2 However, human eyes are always in motion during fixation,3,4,5,6 so retinal neurons receive temporal modulations that depend on the interaction of the spatial structure of the stimulus with eye movements. It has long been hypothesized that these modulations might contribute to spatial encoding,7,8,9,10,11,12 a proposal supported by several recent observations.13,14,15,16 A fundamental, yet untested, consequence of this encoding strategy is that spatial tuning is not hard-wired in the visual system but critically depends on how the fixational motion of the eye shapes the temporal structure of the signals impinging onto the retina. Here we used high-resolution techniques for eye-tracking17 and gaze-contingent display control18 to quantitatively test this distinctive prediction. We examined how contrast sensitivity, a hallmark of spatial vision, is influenced by fixational motion, both during normal active fixation and when the spatiotemporal stimulus on the retina is altered to mimic changes in fixational control. We showed that visual sensitivity closely follows the strength of the luminance modulations delivered within a narrow temporal bandwidth, so changes in fixational motion have opposite visual effects at low and high spatial frequencies. By identifying a key role for oculomotor activity in spatial selectivity, these findings have important implications for the perceptual consequences of abnormal eye movements, the sources of perceptual variability, and the function of oculomotor control.

Inter-Ocular Fixation Instability of Amblyopia: Relationship to Visual Acuity, Strabismus, Nystagmus, Stereopsis, Vergence, and Age

PurposeAmblyopia damages visual sensory and ocular motor functions. One manifestation of the damage is abnormal fixational eye movements. Tiny fixation movements are normal; but when these exceed a normal range, the behavior is labeled “fixation instability(FI).” Here we compare FI between normal and amblyopic subjects, and evaluate the relationship between FI and severity of amblyopia, strabismus angle, nystagmus, stereopsis, vergence, and subject age. Design and MethodsFixation Eye Movements were recorded using infra-red video-oculography from 47 controls(15.3±12.2y) and 104 amblyopic subjects(13.3±11.2y) during binocular and monocular viewing. FI and vergence instability were quantified as Bivariate Contour Ellipse Area (BCEA). We also calculated the ratio of FI between the two eyes: right eye/left eye for controls, amblyopic eye/fellow eye for amblyopes. Multiple regression analysis evaluated how FI related to a range of visuo-motor measures. ResultsDuring binocular viewing, the FI of fellow and amblyopic eye, vergence instability and inter-ocular FI ratios were least in anisometropic and most in mixed amblyopia(p<0.05). Each correlated positively with the strabismus angle(p<0.01). During monocular viewing, subjects with deeper amblyopia(p<.01) and larger strabismus angles(p<.05) had higher inter-ocular FI ratios. 27% of anisometropic and >65% of strabismic/mixed amblyopes had nystagmus. Younger age and nystagmus increased FI and vergence instability(p<0.05), but did not affect the Inter-ocular FI ratios(p>0.05). ConclusionsQuantitative recording of perturbed eye movements in children reveal a major functional deficit linked to amblyopia. Imprecise fixation – measured as inter-ocular FI ratios– may be used as a robust marker for amblyopia and strabismus severity.

NURS-11. NEURO-ONCOLOGIC EMERGENCY MANAGEMENT

Abstract BACKGROUND Due to disease location, neuro-oncology patients experience emergencies that are infrequently encountered in general oncology and require unique interventions. Paramount among these emergencies is vasogenic cerebral edema (CE). Urgent and accurate interventions are needed to decrease associated morbidity and mortality. In an educational institution, access to knowledge of next steps is crucial. This prompted further inquiry of best practice into recognition of increasing intracranial pressure (ICP) and management of cerebral edema using a literature review and reflection on institutional experience. METHODS A literature review was conducted using pubmed to identify articles through January 2014. The Key words used in the search included “neuro-ongologic emergencies” “brain herniation management” “cerebral edema. RESULTS The searched yielded 3237 results. Of these, 3236 were excluded. Ten full text articles were relevant and included in the review. In combination with the literature and institutional experience of neuro-oncological emergencies, interventions and outcomes were evaluated to provide recommendations for treatment in the event of an emergency. CONCLUSION CE is not an uncommon finding with malignant brain tumors given disrupted blood brain barrier. This subsequently increases ICP and left unmanaged, can lead to brain herniation. Signs and symptoms can vary depending on tumor location and extent of edema. Most common exam findings to be aware of include headache, nausea, vomiting, altered pupil exam, abnormal eye movements, and altered consciousness. Ultimately surgical intervention may be the definitive treatment, non-surgical management is important. Literature review supported the use of both high dose dexamethasone and hyperosmolar solutions are temporizing measures to decrease CE. Additional measures such as positioning, treatment of pain or fever, are also recommended. Prompt recognition and intervention of CE are crucial to improved patient outcomes. An educational poster with recommendations for best practice when encountering neuro-oncological emergencies will be created. Dissemination of findings will be done at local, national and international levels.

Joubert syndrome caused by a TMEM67 mutation: Genotype-phenotype analysis

Joubert syndrome (JS), a rare neurodevelopmental disorder, is characterized by a unique midbrain- hindbrain malformation known as the molar tooth sign, a distinctive radiological feature. Among the myriad manifestations associated with JS, the most prevalent features encompass hypotonia, ataxia, developmental delay, intellectual disability, abnormal eye movements, and neonatal breathing abnormalities. To date, 29 genes have been identified as contributors to the development of JS. This study aimed to pinpoint a pathogenic variant in JS within an Iranian consanguineous pedigree. We employed whole-exome sequencing (WES) to pinpoint a potential pathogenic variant likely responsible for the condition in an 8-year-old male patient. The WES analysis successfully revealed a novel homozygous missense mutation (c.725A&gt;T; p.Asn242Ile) within exon 8 (NM_153704.6) of the TMEM67 gene. Subsequent validation through Sanger sequencing confirmed the presence of the chr8-93780603A&gt;T mutation. This study elucidated JS within an Iranian family, uncovering a new TMEM67 gene mutation through comprehensive genetic analysis. The identification of this mutation enhances our understanding of the genetic landscape of JS, contributing valuable insights for both clinical diagnosis and future research endeavors.

Anomalies of Midbrain Hindbrain Development: Midbrain Clefts, Cerebellar Nodular Heterotopia with Overlying Dysgenesis, Cerebellar Foliation Disorder, Pontine Tegmental Cap Dysplasia; Joubert Syndrome; Lhermitte Duclos Syndrome. Diagnosis, Classification and Rehabilitation Hypothesis

AbstractMidbrain and hindbrain (MBHB) malformations are a rare group of congenital abnormalities that involve the neural structure of the posterior cranial fossa, leading to significant causes of neurodevelopmental dysfunction. Recent advancements in genetic and neuroimaging technologies have significantly enhanced our understanding of these disorders. The integration of these advances has facilitated a systematic classification of these conditions. A basic understanding of MBHB embryology is fundamental in order to understand the malformations occurring in their structures: MBHB neurons are mainly generated in the neuroepithelium, lining the walls of the fourth ventricle. Moreover, the regional specificity of the neural tube is determined by a combination of transcription factors expressed, organizing the fate of the neighboring regions as well. Clinical features of MBHB malformations are typically nonspecific; some patients may be asymptomatic or may develop neurological symptoms including hypotonia, ataxia, abnormal eye movements, decreased visual attention, cranial nerve deficits, cognitive impairment, and psychiatric symptoms. Many malformations have been described. We proposed the description of some of them, reporting their main morphologic aspects, magnetic resonance imaging (MRI) peculiar signs and their clinical presentation. Midbrain clefts, for example, are malformations characterized by median separation in the ventral midbrain which involves a communication with the cerebral aqueduct giving a “keyhole” shape. Pontine tegmental cap dysplasia, instead, is a rare hindbrain malformation responsible for a nonprogressive neurological disorder and is described with hypoplastic flat ventral pons, hypoplasia of the middle cerebellar peduncles, and hypoplasia and malformation of the worm. Joubert syndrome, cerebellar nodular heterotopia, abnormal cerebellar foliation, and Lhermitte–Duclos disease, also called dysplastic cerebellar gangliocytoma, have been described as well in order to provide a general overview on this diagnostic challenge reporting the most recent findings.

Ocular manifestations and outcomes of OPMD- a report from the national IsrOPMD registry.

This study aims to describe the ocular manifestations, treatment, and prognosis of OPMD patients registered in the national Israel OPMD(IsrOPMD) registry. Data was prospectively collected from patients referred to the IsrOPMD registry from January 2022 to March 2023. This included patient demographics, medical and ocular history, eye exams, eyelid evaluations, visual field exams, and orthoptic evaluations. 30 patients (15 males, mean age 53 years) were treated in the ocular OPMD clinic, predominantly of Bukhari descent (86.6%). The mean visual acuity was 0.06 logMAR. Twenty-one patients (70%) had eye movement problem, mostly in horizontal gaze. 6(20%) patients' complaint about diplopia. Ptosis surgery was performed in 21(70%) patients, with 17(56.7%) patients underwent frontalis sling surgery and 4(13.3%) patients undergoing levator advancement. The mean Margin reflex distance (MRD1) improved post-surgery (2.28 mm vs. 1.58 mm), but 11(36.6%) patients required more than one ptosis surgery. The study contributes valuable insights into the ocular aspects of OPMD. It reveals that OPMD patients often experience a range of ocular symptoms, such as ptosis, abnormalities in eye movements, strabismus, and potentially diplopia, which can significantly impact their quality of life. The findings underscore the importance of regular ophthalmological follow-up for these patients to address these symptoms effectively. The study is significant in contributing to the limited but growing knowledge about the ocular manifestations of OPMD and the management of these symptoms to improve the quality of life for patients suffering from this condition.

Defects of Midbrain/Hindbrain Development: Defects of Anteroposterior and Dorsoventral Patterning

AbstractThe knowledge regarding the midbrain and the hindbrain (MBHB) malformations has been progressively increased in recent years, thanks to the advent of neuroimaging and genetic technologies. Many classifications have been proposed in order to well describe all of these patterns. The most complete and detailed one is based on the genetic and embryologic features that allow an easier and effective knowledge of these disturbs. It categorizes them into four primary groups: (1) Malformations resulting from early anteroposterior and dorsoventral patterning defects or the misspecification of MBHB germinal zones.(2) Malformations linked to later generalized developmental disorders that notably impact the brain stem and cerebellum, with a pathogenesis that is at least partially comprehended.(3) Localized brain malformations significantly affecting the brain stem and cerebellum, with a pathogenesis that is partly or largely understood, encompassing local proliferation, migration, and axonal guidance.(4) Combined hypoplasia and atrophy observed in presumed prenatal-onset degenerative disorders. Regarding diagnosis, brain stem malformations are typically identified during prenatal assessments, particularly when they are linked with anomalies in the cerebellum and cerebrum. Magnetic resonance imaging is the primary neuroimaging method in the evaluation of these malformations. The clinical characteristics of individuals with malformations in the midbrain or hindbrain are generally nonspecific. Common findings at presentation are hypotonia, motor retardation, ataxia, variable degree of intellectual disability, and abnormal eye movement (e.g., nystagmus, abnormal saccades, oculomotor apraxia, strabismus, and abnormal smooth pursuit). The complexity and the number of these MBHB malformations are constantly increasing. We will provide an overview of MBHB disorders, focusing on embryology, genetic, clinical, and neuroradiology features that could be helpful for clinicians and neuroscientist to understand process of these conditions.

Deciphering Cognitive Impairments in Huntington's Disease: A Comparative Study of Stroop Test Variations.

Huntington's disease (HD) is a neurodegenerative disorder marked by cognitive impairment, movement abnormalities, and behavioral disturbances. The Stroop Color Word Test (SCWT) is a widely used tool to detect cognitive decline in HD. Variations in SCWT formats-horizontal (original) and vertical (Golden)-may influence performance, given HD's impact on cognitive and oculomotor abilities. This study aimed to compare the effectiveness of the horizontal and Golden vertical SCWT formats in detecting cognitive decline in HD, and to determine how performance may have been influenced by eye movement abnormalities. Forty-five participants with genetically confirmed HD were recruited. Both SCWT formats were administered to each participant in a counterbalanced fashion. Individual performance of all three sections on each format was standardized across 2 different norms. Raw and normed scores on each variation were compared and correlated with eye movement ratings on the Unified Huntington's Disease Rating Scale. The Golden variation elicited significantly slower responses, particularly in the Word Reading section, across two benchmark norms. Statistical analysis revealed significant performance differences between the two formats. Correlations between vertical eye movement ratings and performance on the Golden SCWT were highly significant, highlighting the impact of oculomotor coordination on cognitive assessments in HD. This study underscores the importance of considering test format in cognitive assessments for HD. The Golden vertical SCWT demonstrates increased sensitivity in detecting deficits in HD, possibly linked to vertical saccade abnormalities. These insights are important for improving the sensitivity of cognitive assessments and monitoring disease progression in HD research and clinical practice.

Clinical analysis and literature review of two paediatric cases of anti-IgLON5 antibody-related encephalitis.

Anti-IgLON5 antibody-related encephalitis is a rare autoimmune disorder of the central nervous system, predominantly occurring in middle-aged elderly individuals, with paediatric cases being exceptionally rare. This study aims to enhance the understanding of paediatric anti-IgLON5 antibody-related encephalitis by summarising its clinical and therapeutic characteristics. A retrospective analysis was conducted on two paediatric patients diagnosed with anti-IgLON5 antibody-related encephalitis at Hunan Children's Hospital from August 2022 to November 2023. This involved reviewing their medical records and follow-up data, in addition to a literature review. The study involved two patients, one male and one female, aged between 2.5 and 9.6 years, both presenting with an acute/subacute course of illness. Clinically, both exhibited movement disorders (including dystonia, involuntary movements, and ataxia), cognitive impairments, sleep disturbances, and psychiatric symptoms. Patient 1 experienced epileptic seizures, while Patient 2 exhibited brainstem symptoms and abnormal eye movements. Neither patient showed autonomic dysfunction. Patient 1 had normal cerebrospinal fluid (CSF) and Brain MRI findings, whereas Patient 2 showed moderate leukocytosis and mild protein elevation in the CSF, and Brain MRI revealed symmetrical lesions in the basal ganglia and cerebellum. Oligoclonal bands in the CSF were positive in both cases. Both patients tested negative for HLA-DQB*05:01 and HLA-DRB*10:01. They received both first-line and second-line immunotherapies, with Patient 2 showing a poor response to treatment. Paediatric cases of anti-IgLON5 antibody-related encephalitis similarly present sleep disturbances as a core symptom, alongside various forms of movement disorders. Immunotherapy is partially effective. Compared to adult patients, these paediatric cases tend to exhibit more pronounced psychiatric symptoms, a more rapid onset, and more evident inflammatory changes in the CSF. The condition appears to have a limited association with HLA-DQB*05:01 and HLA-DRB*10:01 polymorphisms.

A late-preterm neonate with germinal matrix hemorrhages and rapidly resolving abnormal vertical eye movements

A late-preterm neonate with germinal matrix hemorrhages and rapidly resolving abnormal vertical eye movements