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PURPOSE: To assess the risk of dementia in individuals with newly diagnosed ocular motor cranial neuropathy (OMCN). DESIGN: A nationwide, population-based cohort study using authenticated data from the Korean National Health Insurance Service (KNHIS). PARTICIPANTS: This study included 60 781 patients with OMCN who received a diagnosis between 2010 and 2017 and were followed up through 2018, with an average follow-up of 3.37 ± 2.21 years with a 1-year lag. After excluding patients with disease related to oculomotor dysfunction preceding the OMCN diagnosis, a total of 52 076 patients with OMCN were established. Of these, 23 642 patients who had participated in the National Health Screening Program (NHSP) within 2 years before the OMCN diagnosis were included. After applying the exclusion criteria, the final cohort comprised 19 243 patients and 96 215 age and sex-matched control participants without OMCN. METHODS: We identified patients with newly diagnosed OMCN in the KNHIS database and collected participant characteristics from the health checkup records of the NHSP. The study end point was determined by the first claim with a dementia diagnostic code and antidementia medications. The association of OMCN with dementia risk was examined using Cox proportional hazards regression analysis, adjusting for potential confounding factors. MAIN OUTCOME MEASURES: The main outcome measures were hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause dementia (ACD), Alzheimer's disease (AD), and vascular dementia (VaD) development in patients with OMCN relative to those without OMCN. RESULTS: Patients with newly diagnosed OMCN demonstrated higher metabolic comorbidities than those without OMCN. New OMCN was associated with an elevated risk of ACD (HR, 1.203; 95% CI, 1.113-1.300), AD (HR, 1.137; 95% CI, 1.041-1.243), and VaD (HR, 1.583; 95% CI, 1.286-1.948), independent of potential confounding factors. The younger age groups exhibited a stronger association between OMCN and ACD (HR, 8.690 [< 50 years] vs. 1.192 [≥ 50 years]; P = 0.0004; HR, 2.517 [< 65 years] vs. 1.099 [≥ 65 years]; P < 0.0001). CONCLUSIONS: This nationwide population-based study assessed the association between OMCN and dementia risk. Our results demonstrated a robust relationship between OMCN and the risk of dementia, particularly in the younger population. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.
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Doença de Alzheimer , Doenças dos Nervos Cranianos , Humanos , Criança , Estudos de Coortes , Estudos Retrospectivos , Fatores de Risco , Doença de Alzheimer/diagnósticoRESUMO
BACKGROUND AND PURPOSE: Diagnosis of lymphoma involving the central nervous system (CNS) is challenging. This study aimed to explore the abnormal vestibular and ocular motor findings in CNS lymphoma. METHODS: A retrospective search of the medical records identified 30 patients with CNS lymphoma presenting ocular motor and vestibular abnormalities from four neurology clinics of university hospitals in South Korea (22 men, age range 14-81 years, mean 60.6 ± 15.2). The demographic and clinical features and the results of laboratory, radiological and pathological evaluation were analyzed. RESULTS: Patients presented with diplopia (13/30, 43%), vestibular symptoms (15/30, 50%) or both (2/30, 7%). In 15 patients with diplopia, abnormal ocular motor findings included ocular motor nerve palsy (n = 10, 67%), internuclear ophthalmoplegia (n = 2, 13%), external ophthalmoplegia (n = 2, 13%) and exophoria (n = 1, 7%). The vestibular abnormalities were isolated in 14 (82%) of 17 patients with vestibular symptoms and included combined unilateral peripheral and central vestibulopathy in three from lesions involving the vestibular nuclei. CNS lymphoma involved the brainstem (53%), cerebellum (33%), leptomeninges (30%), deep gray nuclei (23%) or cranial nerves (17%). Two patients showed the "double-panda" sign by involving the midbrain. CONCLUSIONS: This study expands the clinical and radiological spectra of CNS lymphoma. Neuro-ophthalmological and neuro-otological evaluation may guide the early diagnosis of CNS lymphoma.
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Diplopia , Transtornos da Motilidade Ocular , Masculino , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Retrospectivos , Transtornos da Motilidade Ocular/diagnóstico , Movimentos Oculares , Cerebelo , ParalisiaRESUMO
INTRODUCTION: Early Exercise Intolerance (EEI) is associated with delayed recovery and longer time to Return To Play (RTP), but this has not been established.Participants; (n = 52, male n = 30) UK university-aged rugby-union student-athletes. METHODS: Student-athletes completed baseline screening (July-October 2021 and 2022). The test battery was repeated within 48 h, 4, 8 and 14 days after a Sports-Related Concussion (SRC) with the Buffalo Concussion Bike or Treadmill Test to set sub-symptom heart rate threshold. Student-athletes then completed a controlled early exercise protocol in-between reassessment (days 3, 5-7 and 9-13). Those with EEI were compared to those with early-exercise tolerance. OUTCOME MEASURES: Post-Concussion Symptom Scale, Immediate Post-Concussion and Cognitive Test, Vestibular-Ocular Motor Screening Tool and the Revised Perceived Academic Impact Tool. RESULTS: EEI was seen throughout the initial 14-days post-SRC (23.8%, 22.4%, 25.5%. 25.0%). EEI was associated with a slower reaction time within 48 h (-0.01 (-0.030-0.043) Vs 0.06 (0.033-0.24), p = 0.004) and greater VOMS scores within 48 h; (0.00 (0.00-4.00) Vs 5.50 (2.75-9.00), p = 0.016) and 4 days (0.00 (0.00-2.00) Vs 5.00 (0.00-6.00), p = 0.044). RTP was 12.5 days longer in those with EEI at 14-days post-SRC. CONCLUSION: EEI is prevalent following an SRC in university-aged student-athletes and was associated with delayed recovery and RTP.
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Background and Objective: Understanding whether cranial nerve palsy (CNP) acts as an independent risk factor for kidney cancer could have important implications for patient care, early detection, and potentially the development of preventive strategies for this type of cancer in individuals with CNP. This study aimed to examine the risk of kidney cancer following the onset of ocular motor CNP and assess whether CNP could be considered an independent risk factor for kidney cancer. Materials and Methods: A population-based cohort study was conducted using data from the National Sample Cohort (NSC) database of Korea's National Health Insurance Service which was collected from 2010 to 2017. Follow-up was until kidney cancer development, death, or 31 December 2018. Cox proportional hazard regression analysis was performed to determine hazard ratios (HRs) for kidney cancer according to CNP status. Participants aged 20 years or more diagnosed with CNP from 2010 to 2017 were included. Exclusions comprised individuals with specific pre-existing conditions, inability to match a control group, and missing data, among others. CNP patients were age-sex matched in a 1:5 ratio with control cases. The primary outcome was incidence of kidney cancer during the follow-up period. Results: This study comprised 118,686 participants: 19,781 in the CNP group, and 98,905 in the control group. Compared to the control group, participants with CNP had a higher risk of kidney cancer (adjusted HR in model 4, 1.599 [95% CI, 1.116-2.29]). After a 3-year lag period, the CNP group had a significantly higher risk (adjusted HR in model 4, 1.987 [95% CI, 1.252-3.154]). Conclusions: Ocular motor CNP may be an independent risk factor for kidney cancer, as indicated by a higher incidence of kidney cancer in CNP patients. Further research is needed to elucidate the underlying mechanisms and explore potential preventive measures for kidney cancer in patients with ocular motor CNP.
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Doenças dos Nervos Cranianos , Neoplasias Renais , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Renais/epidemiologia , Adulto , Fatores de Risco , República da Coreia/epidemiologia , Idoso , Estudos de Coortes , Doenças dos Nervos Cranianos/epidemiologia , Doenças dos Nervos Cranianos/etiologia , Incidência , Modelos de Riscos ProporcionaisRESUMO
Visual snow syndrome (VSS) is a neurological disorder characterized by a range of continuous visual disturbances. Little is known about the functional pathological mechanisms underlying VSS and their effect on brain network topology, studied using high-resolution resting-state (RS) 7 T MRI. Forty VSS patients and 60 healthy controls underwent RS MRI. Functional connectivity matrices were calculated, and global efficiency (network integration), modularity (network segregation), local efficiency (LE, connectedness neighbors) and eigenvector centrality (significance node in network) were derived using a dynamic approach (temporal fluctuations during acquisition). Network measures were compared between groups, with regions of significant difference correlated with known aberrant ocular motor VSS metrics (shortened latencies and higher number of inhibitory errors) in VSS patients. Lastly, nodal co-modularity, a binary measure of node pairs belonging to the same module, was studied. VSS patients had lower modularity, supramarginal centrality and LE dynamics of multiple (sub)cortical regions, centered around occipital and parietal lobules. In VSS patients, lateral occipital cortex LE dynamics correlated positively with shortened prosaccade latencies (p = .041, r = .353). In VSS patients, occipital, parietal, and motor nodes belonged more often to the same module and demonstrated lower nodal co-modularity with temporal and frontal regions. This study revealed reduced dynamic variation in modularity and local efficiency strength in the VSS brain, suggesting that brain network dynamics are less variable in terms of segregation and local clustering. Further investigation of these changes could inform our understanding of the pathogenesis of the disorder and potentially lead to treatment strategies.
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Encéfalo , Transtornos da Visão , Humanos , Encéfalo/diagnóstico por imagem , Imageamento por Ressonância Magnética , Lobo Occipital , Lobo ParietalRESUMO
A precise sequence of axon guidance events is required for the development of the ocular motor system. Three cranial nerves grow toward, and connect with, six extraocular muscles in a stereotyped pattern, to control eye movements. The signaling protein alpha2-chimaerin (α2-CHN) plays a pivotal role in the formation of the ocular motor system; mutations in CHN1, encoding α2-CHN, cause the human eye movement disorder Duane Retraction Syndrome (DRS). Our research has demonstrated that the manipulation of α2-chn signaling in the zebrafish embryo leads to ocular motor axon wiring defects, although the signaling cascades regulated by α2-chn remain poorly understood. Here, we demonstrate that several cytoskeletal regulatory proteins-collapsin response mediator protein 2 (CRMP2; encoded by the gene dpysl2), stathmin1, and stathmin 2-bind to α2-CHN. dpysl2, stathmin1, and especially stathmin2 are expressed by ocular motor neurons. We find that the manipulation of dpysl2 and of stathmins in zebrafish larvae leads to defects in both the axon wiring of the ocular motor system and the optokinetic reflex, impairing horizontal eye movements. Knockdowns of these molecules in zebrafish larvae of either sex caused axon guidance phenotypes that included defasciculation and ectopic branching; in some cases, these phenotypes were reminiscent of DRS. chn1 knock-down phenotypes were rescued by the overexpression of CRMP2 and STMN1, suggesting that these proteins act in the same signaling pathway. These findings suggest that CRMP2 and stathmins signal downstream of α2-CHN to orchestrate ocular motor axon guidance and to control eye movements.SIGNIFICANCE STATEMENT The precise control of eye movements is crucial for the life of vertebrate animals, including humans. In humans, this control depends on the arrangement of nerve wiring of the ocular motor system, composed of three nerves and six muscles, a system that is conserved across vertebrate phyla. Mutations in the protein alpha2-chimaerin have previously been shown to cause eye movement disorders (squint) and axon wiring defects in humans. Our recent work has unraveled how alpha2-chimaerin coordinates axon guidance of the ocular motor system in animal models. In this article, we demonstrate key roles for the proteins CRMP2 and stathmin 1/2 in the signaling pathway orchestrated by alpha2-chimaerin, potentially giving insight into the etiology of eye movement disorders in humans.
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Orientação de Axônios/fisiologia , Quimerina 1/metabolismo , Neurônios Motores/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Músculos Oculomotores/inervação , Estatmina/metabolismo , Proteínas de Peixe-Zebra/metabolismo , Animais , Quimerina 1/genética , Síndrome da Retração Ocular/genética , Movimentos Oculares , Transdução de Sinais/fisiologia , Peixe-ZebraRESUMO
Eye movements serve vision in orienting gaze toward an object of interest in order to place its image simultaneously on both foveas and in stabilizing gaze relative to the environment in order to maintain fixation on the object of interest, even in the case of body displacement. Disorders of eye movements can interfere with ocular alignment and/or monocular motility, and result in diplopia, which is the most common symptom. Eye movement disorders can also interfere with binocular motility without ocular misalignment and result in gaze palsy. Finally, disorders of eye movement can interfere with ocular stability during fixation or body displacement and result in oscillopsia, which is an illusion of an unstable visual world. A systematic examination of eye movements should be part of the neurological exam in order to detect asymptomatic manifestations that can help for the diagnosis of multiple neurological pathologies. In the case of eye movement disorders, the goals of the examination are to precisely characterize the disorder of motility, alignment, or stability, in order to finally localize anatomically the lesion among the peripheral ocular motor system or the more complex central eye movement neural network and suggest mechanisms and etiologies. In this review, we are describing the standard methods of ocular motor examination, including a "general" approach to any ocular motor assessment, and also the specific approaches to evaluating ocular misalignment, difficulty moving both eyes, and finally unstable gaze. This article will include practical tips on how to perform the tests most effectively or how to interpret the clinical signs elicited.
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Movimentos Oculares , Transtornos da Motilidade Ocular , Fixação Ocular , Humanos , Exame Neurológico , Transtornos da Motilidade Ocular/diagnóstico , Transtornos da Motilidade Ocular/etiologia , Transtornos da VisãoRESUMO
This study aimed to assess the associations between liver enzymes including γ-glutamyl transferase (GGT) and the development of ocular motor cranial nerve palsy (CNP) using the National Sample Cohort database from Korea's National Health Insurance Service. We analyzed data from 4,233,273 medical screening examinees aged 20 years or more in 2009. Study participants were followed up until December 31, 2018. A Cox proportional hazard regression analysis was performed for quartiles of liver enzymes to determine the linkage between each value and ocular motor CNP using quartile 1 as a reference after adjusting for potential confounders. A total of 5,807 (0.14%) patients developed ocular motor CNP during the follow-up period of 8.22 ± 0.94 years. The incidence of ocular motor CNP gradually increased as the GGT levels increased. The highest quartile of the GGT group had hazard ratio (HR) of 1.245 (95% confidence interval [CI], 1.136-1.365). Regarding alanine aminotransferase (ALT), the highest quartile of the ALT group had HR of 1.141 (95% CI, 1.049-1.241). However, the incidence of ocular motor CNP did not gradually increase as the ALT levels increased. The coexistence of the increased level of GGT, metabolic syndrome, and obesity showed a stronger association with ocular motor CNP development (HR, 1.331; 95% CI, 1.173, 1.511) compared to having a single factor or two factors. In conclusion, our population-based cohort study demonstrated a significant association between serum GGT level and the incidence of ocular motor CNP, suggesting that GGT could be a new clinical marker for predicting the occurrence of ocular motor CNP.
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Doenças dos Nervos Cranianos , gama-Glutamiltransferase , Alanina Transaminase , Estudos de Coortes , Doenças dos Nervos Cranianos/complicações , Doenças dos Nervos Cranianos/epidemiologia , Humanos , Fígado , Fatores de RiscoRESUMO
BACKGROUND: Physiological differences between a maturing and matured brain alters how Sports-Related Concussion (SRC) affects different age groups; therefore, a review specific to university-aged student-athletes is needed. OBJECTIVES: Determine time to recovery for symptom burden, neurocognitive and Vestibular-Ocular-Motor (VOM) function and academic impact in university-aged student-athletes. METHODS: Searches were conducted in PubMed, SpringerLink, PsycINFO, Science Direct, Scopus, Cochrane, Web of Science and EMBASE. Articles were included if they contained original data collected within 30 days in university-aged student-athletes, analysed SRC associated symptoms, neurocognitive or VOM function or academic ability and published in English. Two reviewers independently reviewed sources, using the Oxford Classification of Evidence-Based Medicine (CEBM) and the Downs and Black checklist, and independently extracting data before achieving consensus. RESULTS: 58 articles met the inclusion criteria. Recovery of symptoms occurred by 7 and 3-5.3 days for neurocognition. The evidence base did not allow for a conclusion on recovery time for VOM function or academic ability. Few papers investigated recovery times at specified re-assessment time-points and have used vastly differing methodologies. CONCLUSIONS: To fully understand the implication of SRC on the university-aged student-athlete' studies using a multi-faceted approach at specific re-assessments time points are required.Systematic review registration number: CRD42019130685.
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Traumatismos em Atletas , Concussão Encefálica , Idoso , Atletas , Traumatismos em Atletas/complicações , Traumatismos em Atletas/diagnóstico , Concussão Encefálica/complicações , Concussão Encefálica/diagnóstico , Humanos , Estudantes , UniversidadesRESUMO
Early-onset ataxia with ocular motor apraxia and hypoalbuminemia (EAOH) is a neurodegenerative disorder caused by mutation in the aprataxin (APTX)-coding gene APTX, which is involved in DNA single-strand break repair (SSBR). The neurological abnormalities associated with EAOH are similar to those observed in patients with ataxia-telangiectasia. However, the immunological abnormalities in patients with EAOH have not been described. In this study, we report that EAOH patients have immunological abnormalities, including lymphopenia; decreased levels of CD4+ T-cells, CD8+ T-cells, and B-cells; hypogammaglobulinemia; low T-cell recombination excision circles and kappa-deleting element recombination circles; and oligoclonality of T-cell receptor ß-chain variable repertoire. These immunological abnormalities vary among the EAOH patients. Additionally, mild radiosensitivity in the lymphocytes obtained from the patients with EAOH was demonstrated. These findings suggested that the immunological abnormalities and mild radiosensitivity evident in patients with EAOH could be probably caused by the DNA repair defects.
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Apraxias/imunologia , Ataxia Cerebelar/congênito , Hipoalbuminemia/imunologia , Adolescente , Adulto , Apraxias/genética , Apraxias/metabolismo , Estudos de Casos e Controles , Ataxia Cerebelar/genética , Ataxia Cerebelar/imunologia , Ataxia Cerebelar/metabolismo , Criança , Quebras de DNA de Cadeia Simples , Reparo do DNA/genética , Reparo do DNA/efeitos da radiação , Proteínas de Ligação a DNA/genética , Feminino , Genes Codificadores dos Receptores de Linfócitos T , Variação Genética , Humanos , Hipoalbuminemia/genética , Hipoalbuminemia/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Proteínas Nucleares/genética , Tolerância a Radiação/genética , Tolerância a Radiação/imunologia , Linfócitos T/imunologia , Adulto JovemRESUMO
PURPOSE: This study aimed to delineate the genetic basis of congenital ocular motor apraxia (COMA) in patients not otherwise classifiable. METHODS: We compiled clinical and neuroimaging data of individuals from six unrelated families with distinct clinical features of COMA who do not share common diagnostic characteristics of Joubert syndrome or other known genetic conditions associated with COMA. We used exome sequencing to identify pathogenic variants and functional studies in patient-derived fibroblasts. RESULTS: In 15 individuals, we detected familial as well as de novo heterozygous truncating causative variants in the Suppressor of Fused (SUFU) gene, a negative regulator of the Hedgehog (HH) signaling pathway. Functional studies showed no differences in cilia occurrence, morphology, or localization of ciliary proteins, such as smoothened. However, analysis of expression of HH signaling target genes detected a significant increase in the general signaling activity in COMA patient-derived fibroblasts compared with control cells. We observed higher basal HH signaling activity resulting in increased basal expression levels of GLI1, GLI2, GLI3, and Patched1. Neuroimaging revealed subtle cerebellar changes, but no full-blown molar tooth sign. CONCLUSION: Taken together, our data imply that the clinical phenotype associated with heterozygous truncating germline variants in SUFU is a forme fruste of Joubert syndrome.
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Síndrome de Cogan , Proteínas Hedgehog , Apraxias/congênito , Proteínas Hedgehog/genética , Humanos , Fatores de Transcrição Kruppel-Like , Proteínas RepressorasRESUMO
OBJECTIVE: To characterize ocular motor function in patients with Niemann-Pick disease type C (NPC). METHODS: In a multicontinental, cross-sectional study we characterized ocular-motor function in 72 patients from 12 countries by video-oculography. Interlinking with disease severity, we also searched for ocular motor biomarkers. Our study protocol comprised reflexive and self-paced saccades, smooth pursuit, and gaze-holding in horizontal and vertical planes. Data were compared with those of 158 healthy controls (HC). RESULTS: Some 98.2% of patients generated vertical saccades below the 95% CI of the controls' peak velocity. Only 46.9% of patients had smooth pursuit gain lower than that of 95% CI of HC. The involvement in both downward and upward directions was similar (51°/s (68.9, [32.7-69.3]) downward versus 78.8°/s (65.9, [60.8-96.8]) upward). Horizontal saccadic peak velocity and latency, vertical saccadic duration and amplitude, and horizontal position smooth pursuit correlated best to disease severity. Compensating strategies such as blinks to elicit saccades, and head and upper body movements to overcome the gaze palsy, were observed. Vertical reflexive saccades were more impaired and slower than self-paced ones. Gaze-holding was normal. Ocular-motor performance depended on the age of onset and disease duration. CONCLUSIONS: This is the largest cohort of NPC patients investigated for ocular-motor function. Vertical supranuclear saccade palsy is the hallmark of NPC. Vertical upward and downward saccades are equally impaired. Horizontal saccadic peak velocity and latency, vertical saccadic duration and amplitude, and horizontal position smooth pursuit can be used as surrogate parameters for clinical trials. Compensating strategies can contribute to establishing a diagnosis.
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Doença de Niemann-Pick Tipo C , Estudos Transversais , Movimentos Oculares , Humanos , Estudos Prospectivos , Movimentos SacádicosRESUMO
Introduction: Research indicates Sports-Related Concussion (SRC) impairs Vestibular-Ocular-Motor (VOM) function. The aim was to explore if VOM impairment correlates with longer Return To Play (RTP), symptom burden, neurocognitive performance and academic capability.Participants: 40 (61.4% male) Loughborough University, UK, rugby union student-athletes who sustained 42 SRCs.Methods: Student-athletes completed an assessment battery during pre-season (baseline), 2, 4, 8 and 14 days post-SRC and prior to RTP and were managed according to the rugby Football Union' community pathway.Outcome measures: Vestibular Ocular-Motor Screening (VOMS), Immediate Post-Concussion Assessment and Cognitive Test, Post-Concussion Symptom Scale, Perceived Academic Impairment Tool questionnaire and percentage of academic activities specifically missed due to SRC.Results: VOMS scores were significantly (p < 0.005) greater than baseline at all time points except RTP. Presence of VOM dysfunction at 14 days post-SRC significantly correlated with a longer RTP, greater symptom burden and increased odds ratio at 2, 4 and 8 days and academic time loss at 2, 4 and 8 days post-SRC.Conclusion: VOM impairment is associated with an increased symptom burden and impaired academic capability, and a longer time to RTP when present at 14 days post-SRC.
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Traumatismos em Atletas , Concussão Encefálica , Atletas , Traumatismos em Atletas/complicações , Concussão Encefálica/complicações , Feminino , Humanos , Masculino , Volta ao Esporte , EstudantesRESUMO
PRIMARY OBJECTIVE: - To discuss how the underlying neuroanatomy and neurobiology of five sport-related concussion (SRC) clinical profiles impacts assessment and treatment. RESEARCH DESIGN: - Narrative review. METHODS AND PROCEDURES: - Based on the current literature and clinical experience, arguments against the traditional SRC protocol and for a clinical profiles-based SRC protocol are made. MAIN OUTCOMES AND RESULTS: - While the clinical profiles-based SRC protocol is widely used and accepted, there has been little published regarding the link to the underlying neuropathology. Our narrative review describes the five SRC clinical profiles: vestibular, ocular, mood, post-traumatic migraine, and cognitive/fatigue. For these profiles, the underlying neuroanatomy and neurobiology is outlined, as well as how that anatomy and biology impact the profiles' etiology, assessment, and treatment. The cervical and sleep modifiers are also briefly covered. CONCLUSIONS: - Utilizing this model, clinicians are able to provide an individualized assessment, conceptualization, and treatment plan for SRC, leading to improved outcomes and clinical experiences for athletes.
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Traumatismos em Atletas , Concussão Encefálica , Esportes , Atletas , Traumatismos em Atletas/complicações , Traumatismos em Atletas/diagnóstico , Traumatismos em Atletas/terapia , Concussão Encefálica/diagnóstico , Concussão Encefálica/terapia , Humanos , SonoRESUMO
Mild clinical phenotypes of ataxia-telangiectasia (variant A-T) are associated with biallelic ATM variants resulting in residual function of the ATM kinase. At least one regulatory, missense, or leaky splice site mutation resulting in expression of ATM with low level kinase activity was identified in subjects with variant A-T. Studies on the pathogenicity of the germline splicing ATM variant c.1066-6T>G have provided conflicting results. Using whole-exome sequencing, we identified two splice site ATM variants, c.1066-6T>G; [p.?], and c.2250G>A, [p.Ile709_Lys750del], in a compound heterozygous state in a 27-year-old woman who had been diagnosed as having congenital ocular motor apraxia type Cogan in her childhood. Reappraisal of her clinical phenotype revealed consistency with variant A-T. Functional analyses showed reduced expression of ATM protein and residual activity of the ATM kinase at a level consistent with variant A-T. Our results provide evidence for pathogenicity of the leaky ATM splice site variant c.1066-6T>G.
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Proteínas Mutadas de Ataxia Telangiectasia/genética , Ataxia Telangiectasia/patologia , Predisposição Genética para Doença , Mutação , Splicing de RNA/genética , Adulto , Ataxia Telangiectasia/genética , Feminino , Humanos , FenótipoRESUMO
PURPOSE OF REVIEW: To provide an overview of vestibular lab testing and to familiarize the reader with common results observed in headache patients with dizziness. RECENT FINDINGS: The latest research indicates variable levels of both peripheral and central vestibular dysfunction in headache populations with dizziness. Mechanisms may include vestibulocerebellar loss of inhibition, central vestibular network misfiring, and peripheral pathology aggravating central hypersensitization. Headache patients are commonly affected by dizziness stemming from various etiologies. Although history is still the gold standard in diagnosis, vestibular lab testing can identify the integrity of vestibular function. Research is emerging and future directions are encouraging.
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Tontura , Transtornos de Enxaqueca , Tontura/diagnóstico , Tontura/etiologia , Cefaleia/diagnóstico , Cefaleia/etiologia , Humanos , VertigemRESUMO
Intraoperative monitoring systems that utilize various evoked potentials for the detection and/or preservation of cranial nerves have become increasingly common due to recent technical and commercial developments, particularly during skull base surgeries. We established a novel system for the intraoperative monitoring of the extraocular motor nerves (eOMNs) using a piezoelectric device capable of detecting imperceptible vibrations induced by ocular movement, with sensors placed on the eyelids alone. We first evaluated the efficacy and reliability of this device for the intraoperative monitoring of eOMNs in two Beagle dogs. Based on the results, we then determined the appropriate stimulation parameters for use in human surgical cases involving removal of various skull base tumors. Animal experiments revealed that a 0.4 mA monopolar electrical stimulation was required to elicit significant responses and that these responses were not inferior to those obtained via the electrooculogram/electromyogram. Significant responses were also detected in preliminary clinical investigations in human patients, following both direct and indirect monopolar electrical stimulation of the oculomotor and abducens nerves, although obtaining responses from the trochlear nerve was difficult. Intraoperative monitoring using a piezoelectric device provides a simple and reliable method for detecting eOMNs, especially the oculomotor and abducens nerves. This monitoring system can be adapted to various surgeries for skull base tumor.
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Nervos Cranianos/fisiopatologia , Movimentos Oculares/fisiologia , Monitorização Intraoperatória/métodos , Procedimentos Neurocirúrgicos , Base do Crânio/cirurgia , Animais , Cães , Estimulação Elétrica , Eletromiografia , Potenciais Evocados , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Neoplasias da Base do Crânio/cirurgiaRESUMO
BACKGROUND: Ocular motor dysfunction is one of the most common postoperative complications of petroclival meningioma. However, its incidence, recovery rate, and independent risk factors remain poorly explored. METHODS: A prospective analysis of 31 petroclival meningiomas was performed. Operative approaches were selected by utilizing a new 6-region classification of petroclival meningiomas we proposed. Two scores were used to evaluate the functions of the oculomotor and abducens nerves. Pearson correlation analysis and binary logistic regression analysis were used to identify independent risk factors for intraoperative oculomotor and abducens nerve injury. RESULTS: Postoperative new-onset dysfunctions in the pupillary light reflex and eye/eyelid movements as well as abducens paralysis were detected in eight (25.8%), ten (32.3%) and twelve (38.7%) cases, respectively. Their corresponding recovery rates after 6 months of follow-up were 75% (6/8), 80% (8/10), and 83.3% (10/12), respectively, and their mean times to start recovery were 4.03, 2.43, and 2.5 months, respectively. Tumor invasion into the suprasellar region/sphenoid sinus was the only risk factor for dysfunctions in both the pupillary light reflex (p = 0.001) and eye/eyelid movements (p = 0.002). Intraoperative utilization of the infratrigeminal interspace was the only risk factor for dysfunction in eyeball abduction movement (p = 0.004). CONCLUSIONS: Dysfunctions of the oculomotor and abducens nerves recovered within 6 months postoperatively. Tumor extension into the suprasellar region/sphenoid sinus was the only risk factor for oculomotor nerve paralysis. Eye/eyelid movements were more sensitive than the pupillary light reflex in reflecting nerve dysfunctions. Intraoperative utilization of the infratrigeminal interspace was the only risk factor for abducens nerve paralysis.
Assuntos
Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Procedimentos Neurocirúrgicos/efeitos adversos , Traumatismos do Nervo Oculomotor/fisiopatologia , Complicações Pós-Operatórias/fisiopatologia , Neoplasias da Base do Crânio/cirurgia , Nervo Abducente/patologia , Traumatismo do Nervo Abducente/etiologia , Traumatismo do Nervo Abducente/fisiopatologia , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Neurocirúrgicos/métodos , Nervo Oculomotor/patologia , Traumatismos do Nervo Oculomotor/etiologia , Complicações Pós-Operatórias/etiologia , Reflexo PupilarRESUMO
PURPOSE: Strabismus or anisometropia disrupts binocularity and results in fixation instability, which is increased with amblyopia. Fixation instability has typically been assessed for each eye individually. Recently, vergence instability was reported in exotropic adults and monkeys during binocular viewing. We evaluated fixation instability during binocular viewing in children treated for anisometropia and/or strabismus. METHODS: 160 children age 4-12 years with treated esotropia and/or anisometropia (98 amblyopic, 62 nonamblyopic) were compared to 46 age-similar controls. Fixation instability was recorded during binocular fixation of a 0.3 deg diameter dot for 20â¯s using a 500â¯Hz remote video binocular eye tracker (EyeLink 1000; SR Research). The bivariate contour ellipse area (BCEA; log deg2) for fixation instability was calculated for each eye (nonpreferred, preferred) and for vergence instability (left eye position - right eye position). Best-corrected visual acuity, Randot Preschool stereoacuity, and extent of suppression scotoma (Worth 4-Dot) were also obtained. RESULTS: When binocularly viewing, both amblyopic and nonamblyopic children treated for anisometropia and/or strabismus had larger fixation instability and vergence instability than controls. Amblyopia primarily added to the instability of the nonpreferred eye. Anisometropic children had less nonpreferred eye instability and vergence instability than those with strabismus or combined mechanism. Nonpreferred eye instability and vergence instability were related to poorer stereoacuity and a larger suppression scotoma. Preferred eye instability was not related to any visual outcome measure. No relationships were found with visual acuity. CONCLUSIONS: Fixation instability and vergence instability during binocular viewing suggests that discordant binocular visual experience during childhood, especially strabismus, interferes with ocular motor development. Amblyopia adds to instability of the nonpreferred eye. Vergence instability may limit potential for recovery of binocular vision in these children.
Assuntos
Ambliopia/fisiopatologia , Anisometropia/fisiopatologia , Movimentos Oculares/fisiologia , Fixação Ocular/fisiologia , Estrabismo/fisiopatologia , Visão Binocular/fisiologia , Acuidade Visual , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Testes de Campo VisualRESUMO
To review our studies and "top-down" models of saccadic intrusions and infantile nystagmus syndrome with the aim of hypothesizing areas of cerebellar connections controlling parts of the ocular motor subsystems involved in both types of function and dysfunction. The methods of eye-movement recording and modeling are described in detail in the cited references. Saccadic intrusions, such as square-wave jerks and square-wave oscillations, can be simulated by a single malfunction, whereas staircase saccadic intrusions required two independent malfunctions. The major infantile nystagmus syndrome waveforms are traceable to a failure to calibrate the damping ratio of the smooth pursuit system. The use of a behavioral ocular motor system model demonstrated how putative cerebellar dysfunctions could accurately simulate both the oscillations and the ocular motor responses seen in patients with both saccadic and pursuit disorders.