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PURPOSE: Morning glory disc anomaly (MGDA) is a rare congenital ophthalmologic disorder. Historically it has been diagnosed fundoscopically, with little in the literature regarding its imaging findings. The purpose of this study is to further characterize the orbital and associated intracranial magnetic resonance imaging (MRI) findings of MGDA in our tertiary pediatric center. METHODS: A retrospective review was performed of fundoscopically-diagnosed cases of MGDA, that had been referred for MRI. All MRI studies were scrutinized for orbital and other intracranial abnormalities known to occur in association with MGDA. RESULTS: 18 of 19 cases of MGDA showed three characteristic MRI findings: funnel-shaped morphology of the posterior optic disc, abnormal soft tissue associated with the retrobulbar optic nerve, and effacement of adjacent subarachnoid spaces. The ipsilateral (intraorbital) optic nerve was larger in one patient and smaller in six. The ipsilateral optic chiasm was larger in two patients and smaller in one. CONCLUSION: This study represents a comprehensive radiological-led investigation into MGDA. It describes the most frequently-encountered MRI findings in MGDA and emphasizes the importance of MRI in this cohort, i.e., in distinguishing MGDA from other posterior globe abnormalities, in assessing the visual pathway, and in screening for associated intracranial abnormalities - skull base/cerebral, vascular, and facial. It hypothesizes neurocristopathy as an underlying cause of MGDA and its associations. Caliber abnormalities of the ipsilateral optic nerve and chiasm are a frequent finding in MGDA. Optic pathway enlargement should not be labeled "glioma". (239/250).
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Imagen por Resonancia Magnética , Disco Óptico , Humanos , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Estudios Retrospectivos , Niño , Disco Óptico/anomalías , Disco Óptico/diagnóstico por imagen , Preescolar , Lactante , Adolescente , Anomalías del Ojo/diagnóstico por imagenRESUMEN
An Asian man in his 20s developed asymptomatic ipsilateral moyamoya-like vascular changes following orbital and head trauma. An ipsilateral traumatic optic neuropathy with extensive optic cupping ensued. The complex embryology of the ocular vascular development is reviewed as having a potential causative role in the intracranial carotid vasculopathy.
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BACKGROUND: The tortuosity of the optic nerve can be quantified radiologically by measuring the angle of optic nerve deformation (the "optic nerve angle" [ONA]). In patients with idiopathic intracranial hypertension (IIH), lowering the intracranial pressure (ICP) to a normal range by lumbar puncture leads to straightening of the optic nerve and an increase in the measured sagittal ONA on MRI. It is uncertain whether there is any correlation between ONA and cerebrospinal fluid (CSF) opening pressure or visual function. METHODS: Retrospective study of patients with and without IIH who had MRI of the brain followed by lumbar puncture with CSF opening pressure within 24 hours of MRI. Before LP and within 24 hours of MRI of the brain, all patients with IIH had neuro-ophthalmologic assessment including visual acuity, Humphrey Visual Field (HVF), and fundus photography. Sagittal ONA was measured on multiplanar T2-SPACE images on a DICOM viewer. Papilledema on the fundus photographs was graded using the Frisén scale. RESULTS: Fifty-four patients with IIH and 30 unmatched controls were included. The IIH group was 6.3 years younger (95% CI 2.4-10.3, P = 0.002), had 8.7 kg/m2 higher body mass index (4.9-12.5, P < 0.001), and 26.3% more women (P = 0.011) compared with controls. In both eyes, the ONA was significantly smaller in patients with IIH by 12° compared with controls (7°-17°, P < 0.00001). In the IIH group, no correlation between ONA and the CSF opening pressure was present in either eye (right eye r = 0.19, P = 0.15; left eye r = 0.18, P = 0.19) The ONA did not correlate with logarithm of the minimum angle of resolution visual acuity (right eye r = 0.26, P = 0.063; left eye r = 0.15, P = 0.27), HVF mean deviation (right eye r = 0.0059, P = 0.97; left eye r = -0.069, P = 0.63), or Frisén grade (Spearman's rho right eye 0.058, P = 0.67; left eye 0.14, P = 0.30). CONCLUSIONS: The ONA is significantly smaller in patients with IIH compared to controls, but does not correlate with CSF opening pressure, severity of papilledema, or visual function. The ONA may be useful in identifying patients with raised ICP, but not necessarily those with a poor visual prognosis.
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Hipertensión Intracraneal , Papiledema , Seudotumor Cerebral , Femenino , Humanos , Presión Intracraneal/fisiología , Nervio Óptico/diagnóstico por imagen , Papiledema/diagnóstico , Papiledema/etiología , Seudotumor Cerebral/complicaciones , Seudotumor Cerebral/diagnóstico , Estudios RetrospectivosRESUMEN
AIM: To determine the risk of ocular complications of sildenafil therapy in neonates. METHODS: Retrospective case review of neonates with persistent pulmonary hypertension of the newborn who received sildenafil therapy between 2010 and 2015 in a single, tertiary surgical neonatal intensive care unit in Australia. Ophthalmic examination findings in the neonatal intensive care unit and follow-up were examined. RESULTS: Twenty-seven neonates with persistent pulmonary hypertension of the newborn received sildenafil. The median gestational age (GA) was 38 weeks (range 24-41 weeks), and median birthweight was 2690 g (range 454-4270 g). Ophthalmic review was undertaken in 23 neonates, and 16 neonates were term or near-term infants (GA 31-40 weeks). All of them had a normal initial ophthalmic examination; one child was later diagnosed with hypermetropia and another with infantile esotropia. Amongst the seven premature infants (GA 24-30 weeks), three had retinopathy of prematurity (ROP) diagnosed at the first ophthalmic review and the other four had normal initial examinations. Two patients later developed ROP, one of whom was also diagnosed with congenital motor nystagmus. All five patients diagnosed with ROP were extremely preterm (<28 weeks) with low birthweight (454-635 g). CONCLUSIONS: There were no short-term complications attributable to sildenafil therapy identified in term or near-term neonates (GA ≥31 weeks). This cohort of neonates does not typically undergo ophthalmic review as part of the ROP screening protocol in our institution. Routine ophthalmic review of neonates on sildenafil therapy, who are not at risk of ROP, is therefore unlikely to be warranted. Further research is required to clarify the relationship between sildenafil and ROP.
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Retinopatía de la Prematuridad , Australia , Edad Gestacional , Humanos , Lactante , Recién Nacido , Retinopatía de la Prematuridad/inducido químicamente , Retinopatía de la Prematuridad/diagnóstico , Estudios Retrospectivos , Factores de Riesgo , Citrato de Sildenafil/efectos adversosRESUMEN
BACKGROUND: Organochlorine pesticides are associated with an increased risk of Parkinson's disease. A preliminary analysis from the Honolulu-Asia Aging Study suggested that heptachlor epoxide, a metabolite from an organochlorine pesticide extensively used in Hawaii, may be especially important. This was a cross sectional analysis to evaluate the association of heptachlor epoxide and other organochlorine compounds with Lewy pathology in an expanded survey of brain organochlorine residues from the longitudinal Honolulu-Asia Aging Study. METHODS: Organochlorines were measured in frozen occipital or temporal lobes in 705 brains using gas chromatography with mass spectrometry. Lewy pathology was identified using hematoxylin and eosin- and α-synuclein immunochemistry-stained sections from multiple brain regions. RESULTS: The prevalence of Lewy pathology was nearly doubled in the presence versus the absence of heptachlor epoxide (30.1% versus 16.3%, P < 0.001). Although associations with other compounds were weaker, hexachlorobenzene (P = 0.003) and α-chlordane (P = 0.007) were also related to Lewy pathology. Most of the latter associations, however, were a result of confounding from heptachlor epoxide. Neither compound was significantly related to Lewy pathology after adjustment for heptachlor epoxide. In contrast, the association of heptachlor epoxide with Lewy pathology remained significant after adjustments for hexachlorobenzene (P = 0.013) or α-chlordane (P = 0.005). Findings were unchanged after removal of cases of PD and adjustment for age and other characteristics. CONCLUSIONS: Organochlorine pesticides are associated with the presence of Lewy pathology in the brain, even after exclusion of PD cases. Although most of the association is through heptachlor epoxide, the role of other organochlorine compounds is in need of clarification. © 2018 International Parkinson and Movement Disorder Society.
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Encéfalo/efectos de los fármacos , Epóxido de Heptaclor/farmacología , Hidrocarburos Clorados/farmacología , Enfermedad por Cuerpos de Lewy/etiología , Plaguicidas/farmacología , Anciano , Encéfalo/patología , Estudios Transversales , Cromatografía de Gases y Espectrometría de Masas/métodos , Humanos , Hidrocarburos Clorados/metabolismo , Enfermedad por Cuerpos de Lewy/patología , Masculino , Persona de Mediana Edad , Enfermedad de Parkinson/patologíaRESUMEN
PURPOSE OF REVIEW: To summarize recent developments in the classification, investigation and management of pediatric optic neuritis (PON). RECENT FINDINGS: A recent surge in interest surrounding antibodies to myelin oligodendrocyte glycoprotein antibody (MOG-Ab) has instigated a paradigm shift in our assessment of children with PON. This serological marker is associated with a broad spectrum of demyelinating syndromes that are clinically and radiologically distinct from multiple sclerosis (MS) and aquaporin-4 antibody positive neuromyelitis optica spectrum disorder (AQP4+NMOSD). Optic neuritis is the most common presenting phenotype of MOG-Ab positive-associated disease (MOG+AD). MOG-Ab seropositivity is much more common in the pediatric population and it predicts a better prognosis than MS or AQP4+NMOSD, except in the subset that exhibit a recurrent phenotype. SUMMARY: A better grasp of MOG+AD features and its natural history has facilitated more accurate risk stratification of children after a presenting episode of PON. Consequently, the initial investigation of PON has broadened to include serology, along with neuroimaging and cerebrospinal fluid analysis. Acute treatment of PON and chronic immunotherapy is also becoming better tailored to the suspected or confirmed diagnoses of MS, AQP4+NMOSD and MOG+AD.
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Acuaporina 4/inmunología , Autoanticuerpos/sangre , Glicoproteína Mielina-Oligodendrócito/inmunología , Neuritis Óptica/diagnóstico , Biomarcadores , Niño , Humanos , Esclerosis Múltiple/diagnóstico , Esclerosis Múltiple/inmunología , Neuromielitis Óptica/diagnóstico , Neuromielitis Óptica/inmunología , Neuritis Óptica/inmunología , PronósticoAsunto(s)
Neoplasias de los Nervios Craneales/patología , Neurilemoma/patología , Enfermedades del Nervio Troclear/patología , Neoplasias de los Nervios Craneales/diagnóstico por imagen , Estudios de Seguimiento , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Neurilemoma/diagnóstico por imagen , Enfermedades del Nervio Troclear/diagnóstico por imagenRESUMEN
Selenoproteins are important for normal brain function, and decreased function of selenoproteins can lead to impaired cognitive function and neurological disorders. This review examines the possible roles of selenoproteins in Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and epilepsy. Selenium deficiency is associated with cognitive decline, and selenoproteins may be helpful in preventing neurodegeneration in AD. PD is associated with impaired function of glutathione peroxidase selenoenzymes. In HD, selenium deters lipid peroxidation by increasing specific glutathione peroxidases. Selenium deficiency increases risk of seizures in epilepsy, whereas supplementation may help to alleviate seizures. Further studies on the mechanisms of selenoprotein function will increase our understanding of how selenium and selenoproteins can be used in treatment and prevention of brain disorders.
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Encefalopatías/metabolismo , Selenio/metabolismo , Selenoproteínas/metabolismo , Animales , Encefalopatías/tratamiento farmacológico , Humanos , Selenio/uso terapéuticoRESUMEN
BACKGROUND: During extracorporeal membrane oxygenation (ECMO), circulation of blood across synthetic surfaces triggers an inflammatory response. Therefore, we evaluated the ability of continuous renal replacement therapy (CRRT) to remove cytokines and reduce the inflammatory response in a piglet hemorrhage-reperfusion ECMO model. METHODS: Three groups were studied: (i) uninjured controls (n = 11); (ii) hemorrhage-reperfusion while on venoarterial ECMO (30% hemorrhage with subsequent blood volume replacement within 60 min) (n = 8); (iii) treatment with CRRT after hemorrhage-reperfusion while on ECMO (n = 7). Hemodynamic parameters, oxygen utilization, and plasma and broncho-alveolar lavage (BAL) cytokine levels were recorded and lung tissue samples collected for histologic comparison. RESULTS: Whereas mean arterial pressures decreased among hemorrhage-reperfusion piglets, ECMO with CRRT did not significantly alter mean arterial pressures or systemic vascular resistance and was able to maintain blood flow as well as oxygen delivery after hemorrhage-reperfusion. Plasma interleukin (IL)-6 and IL-10, and BAL tumor necrosis factor (TNF)-α, IL-1ß, IL-6, IL-8, and IL-10 increased as a result of hemorrhage-reperfusion while on ECMO. After a 6-h period of CRRT, plasma IL-6 and BAL TNF-α, IL-6, and IL-8 levels decreased. CONCLUSION: Data suggest CRRT may decrease inflammatory cytokine levels during the initial phase of ECMO therapy following hemorrhage-reperfusion while maintaining cardiac output and oxygen utilization.
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Modelos Animales de Enfermedad , Oxigenación por Membrana Extracorpórea , Inflamación/terapia , Terapia de Reemplazo Renal , Animales , Líquido del Lavado Bronquioalveolar , Citocinas/metabolismo , Hemodinámica , Oxígeno/metabolismo , PorcinosRESUMEN
We present a case of bilateral myelin oligodendrocyte glycoprotein antibody optic neuritis (MOG-ON) with unilateral vitreous hemorrhage in a 6-year-old boy. Multidisciplinary team care, including extensive investigations and prolonged follow-up, excluded alternative causes of vitreous hemorrhage. Early suspicion and diagnosis of MOG-ON led to timely intravenous methylprednisolone treatment, with protracted oral steroid taper, resulting in complete resolution of optic nerve swelling, vitreous hemorrhage, and visual function.
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Neuritis Óptica , Hemorragia Vítrea , Autoanticuerpos , Humanos , Metilprednisolona/uso terapéutico , Glicoproteína Mielina-Oligodendrócito , Neuritis Óptica/diagnóstico , Neuritis Óptica/tratamiento farmacológico , Hemorragia Vítrea/diagnóstico , Hemorragia Vítrea/tratamiento farmacológico , Hemorragia Vítrea/etiologíaRESUMEN
We present the case of an 8-year-old girl with chronic recurrent multifocal osteomyelitis (CRMO) involving the orbit and facial bone and causing left optic neuropathy. She presented with intermittent left periorbital swelling and a history of CRMO diagnosed 5 years earlier. Her disease responded well to adalimumab; however, delayed presentation resulted in permanent unilateral optic nerve atrophy and reduced vision. Orbital inflammatory disease is a rare manifestation of CRMO, and early recognition of the disease and treatment may prevent irreversible vision loss.
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Enfermedades del Nervio Óptico , Osteomielitis , Niño , Enfermedad Crónica , Femenino , Humanos , Nervio Óptico , Enfermedades del Nervio Óptico/diagnóstico , Enfermedades del Nervio Óptico/tratamiento farmacológico , Enfermedades del Nervio Óptico/etiología , Osteomielitis/complicaciones , Osteomielitis/diagnóstico , Osteomielitis/tratamiento farmacológico , Enfermedades RarasRESUMEN
The visual system has high metabolic requirements and is therefore particularly vulnerable to mitochondrial dysfunction. The most commonly affected tissues include the extraocular muscles, photoreceptors, retinal pigment epithelium, optic nerve and visual cortex. Hence, the most common manifestations of mitochondrial disorders are progressive external ophthalmoplegia, macular pattern dystrophy, pigmentary retinopathy, optic neuropathy and retrochiasmal visual field loss. With the exception of Leber hereditary optic neuropathy and stroke-like episodes seen in mitochondrial encephalopathy, lactic acidosis and stroke-like episodes, the majority of neuro-ophthalmic manifestations have an insidious onset. As such, some patients may not recognize subtle progressive visual symptoms. When mitochondrial disorders are highly suspected, meticulous examination performed by an ophthalmologist with targeted ancillary testing can help confirm the diagnosis. Similarly, neuro-ophthalmic symptoms and signs may be the first indication of mitochondrial disease and should prompt systemic investigations for potentially life-threatening associations, such as cardiac conduction defects. Finally, the ophthalmologist can offer symptomatic treatments for some of the most disabling manifestations of these disorders.
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OBJECTIVE: While excessive daytime sleepiness (EDS) can predate the clinical diagnosis of Parkinson disease (PD), associations with underlying PD pathogenesis are unknown. Our objective is to determine if EDS is related to brain Lewy pathology (LP), a marker of PD pathogenesis, using clinical assessments of EDS with postmortem follow-up. METHODS: Identification of LP was based on staining for α-synuclein in multiple brain regions in a sample of 211 men. Data on EDS were collected at clinical examinations from 1991 to 1999 when participants were aged 72-97 years. RESULTS: Although EDS was more common in the presence vs absence of LP (p = 0.034), the association became stronger in neocortical regions. When LP was limited to the olfactory bulb, brainstem, and basal forebrain (Braak stages 1-4), frequency of EDS was 10% (4/40) vs 17.5% (20/114) in decedents without LP (p = 0.258). In contrast, compared to the absence of LP, EDS frequency doubled (36.7% [11/30], p = 0.023) when LP reached the anterior cingulate gyrus, insula mesocortex, and midfrontal, midtemporal, and inferior parietal neocortex (Braak stage 5). With further infiltration into the primary motor and sensory neocortices (Braak stage 6), EDS frequency increased threefold (51.9% [14/27], p < 0.001). Findings were similar across sleep-related features and persisted after adjustment for age and other covariates, including the removal of PD and dementia with Lewy bodies. CONCLUSIONS: The association between EDS and PD includes relationships with extensive topographic LP expansion. The neocortex could be especially vulnerable to adverse relationships between sleep disorders and aggregation of misfolded α-synuclein and LP formation.
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Cuerpos de Lewy/patología , Enfermedad por Cuerpos de Lewy/patología , Enfermedad de Parkinson/patología , Trastornos del Sueño-Vigilia/patología , Anciano , Anciano de 80 o más Años , Encéfalo/patología , Demencia/patología , Trastornos de Somnolencia Excesiva/diagnóstico , Trastornos de Somnolencia Excesiva/patología , Femenino , Humanos , Enfermedad por Cuerpos de Lewy/diagnóstico , Masculino , Enfermedad de Parkinson/diagnóstico , alfa-Sinucleína/metabolismoRESUMEN
A 2.6-year-old boy presented with prominent corneal arcus. This clinical sign is rarely seen at such a young age and led to the diagnosis of familial hypercholesterolemia (FH). Genetic analysis detected biallelic pathogenic sequence variants c.1069G>A and c.2034C>A in the LDLR gene. There is significant cardiovascular morbidity and mortality associated with FH, hence early diagnosis and treatment is imperative.
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Arco Senil/etiología , Córnea/patología , Hiperlipoproteinemia Tipo II/complicaciones , Adulto , Arco Senil/diagnóstico , Arco Senil/genética , Preescolar , LDL-Colesterol/sangre , Femenino , Estudios de Seguimiento , Pruebas Genéticas , Homocigoto , Humanos , Hiperlipoproteinemia Tipo II/sangre , Hiperlipoproteinemia Tipo II/genética , Masculino , FenotipoRESUMEN
Previous studies demonstrated that selenium in the form of sodium selenate reduces neurofibrillary tangle formation in Alzheimer's disease models. Hyperphosphorylation of tau, which leads to formation of neurofibrillary tangles in Alzheimer's disease, is increased by endoplasmic reticulum (ER) stress. Selenoprotein S (SelS) is part of an ER membrane complex that removes misfolded proteins from the ER as a means to reduce ER stress. Selenate, as with other forms of selenium, will increase selenoprotein expression. We therefore proposed that increased SelS expression by selenate would contribute to the beneficial actions of selenate in Alzheimer's disease. SelS expression increased with ER stress and decreased under conditions of elevated glucose concentrations in the SH-SY5Y neuronal cell line. Reducing expression of SelS with siRNA promoted cell death in response to ER stress. Selenate increased SelS expression, which significantly correlated with decreased tau phosphorylation. Restricting SelS expression during ER stress conditions increased tau phosphorylation, and also promoted aggregation of phosphorylated tau in neurites and soma. In human postmortem brain, SelS expression coincided with neurofibrillary tangles, but not with amyloid-ß plaques. These results indicate that selenate can alter phosphorylation of tau by increasing expression of SelS in Alzheimer's disease and potentially other neurodegenerative disorders.
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Encéfalo/metabolismo , Estrés del Retículo Endoplásmico/efectos de los fármacos , Proteínas de la Membrana/farmacología , Selenoproteínas/farmacología , Proteínas tau/metabolismo , Anciano , Anciano de 80 o más Años , Análisis de Varianza , Línea Celular Tumoral , Estrés del Retículo Endoplásmico/fisiología , Regulación de la Expresión Génica/genética , Glucosa/farmacología , Humanos , Leucina/genética , Proteínas de la Membrana/genética , Mutación/genética , Neuroblastoma/patología , Fosforilación/efectos de los fármacos , Prolina/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/genética , ARN Interferente Pequeño/metabolismo , Selenoproteínas/genética , TransfecciónRESUMEN
Cerebrovascular injury while on extracorporeal membrane oxygenation (ECMO) may be caused by excessive brain perfusion during hypoxemic reperfusion. Previous studies have postulated that the most vulnerable period of time for cerebrovascular injury is during the transfer period to ECMO. Therefore, our objective was to compare brain perfusion and hemodynamics in a piglet endotoxic shock ECMO model. The effect of ECMO flow on microcirculation of different brain regions was compared between 10 control pigs and six pigs (7-10 kg) administered IV endotoxin to achieve a drop in mean arterial blood pressure (MAP) of at least 30%. Cardiac output (CO), brain oxygen utilization, and microcirculatory blood flow (BF) were compared at baseline and 2 hours after ECMO stabilization. Matching ECMO delivery with baseline CO in control animals increased perfusion (p < 0.05) in all areas of the brain. In contrast, with endotoxin, ECMO returned perfusion closer to baseline levels in all regions of the brain and maintained brain tissue oxygen consumption. Both control and endotoxic pigs showed no evidence of acute neuronal necrosis in histologic cerebral cortical sections examined after 2 hours of ECMO. Results show that during endotoxic shock, transition to ECMO can maintain brain BF equally to all brain regions without causing overperfusion, and does not appear to cause brain tissue histopathologic changes (hemorrhage or necrosis) during the acute stabilization period after ECMO induction.