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1.
Acta Obstet Gynecol Scand ; 103(2): 322-333, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37984808

RESUMEN

INTRODUCTION: Fetal surgery for open spina bifida (OSB) requires comprehensive preoperative assessment using imaging for appropriate patient selection and to evaluate postoperative efficacy and complications. We explored patient access and conduct of fetal magnetic resonance imaging (MRI) for prenatal assessment of OSB patients eligible for fetal surgery. We compared imaging acquisition and reporting to the International Society of Ultrasound in Obstetrics and Gynecology MRI performance guidelines. MATERIAL AND METHODS: We surveyed access to fetal MRI for OSB in referring fetal medicine units (FMUs) in the UK and Ireland, and two NHS England specialist commissioned fetal surgery centers (FSCs) at University College London Hospital, and University Hospitals KU Leuven Belgium. To study MRI acquisition protocols, we retrospectively analyzed fetal MRI images before and after fetal surgery for OSB. RESULTS: MRI for fetal OSB was accessible with appropriate specialists available to supervise, perform, and report scans. The average time to arrange a fetal MRI appointment from request was 4 ± 3 days (range, 0-10), the average scan time available was 37 ± 16 min (range, 20-80 min), with 15 ± 11 min (range, 0-30 min) extra time to repeat sequences as required. Specific MRI acquisition protocols, and MRI reporting templates were available in only 32% and 18% of units, respectively. Satisfactory T2-weighted (T2W) brain imaging acquired in three orthogonal planes was achieved preoperatively in all centers, and 6 weeks postoperatively in 96% of FSCs and 78% of referring FMUs. However, for T2W spine image acquisition referring FMUs were less able to provide three orthogonal planes presurgery (98% FSC vs. 50% FMU, p < 0.001), and 6 weeks post-surgery (100% FSC vs. 48% FMU, p < 0.001). Other standard imaging recommendations such as T1-weighted (T1W), gradient echo (GE) or echoplanar fetal brain and spine imaging in one or two orthogonal planes were more likely available in FSCs compared to FMUs pre- and post-surgery (p < 0.001). CONCLUSIONS: There was timely access to supervised MRI for OSB fetal surgery assessment. However, the provision of images of the fetal brain and spine in sufficient orthogonal planes, which are required for determining eligibility and to determine the reversal of hindbrain herniation after fetal surgery, were less frequently acquired. Our evidence suggests the need for specific guidance in relation to fetal MRI for OSB. We propose an example guidance for MRI acquisition and reporting.


Asunto(s)
Espina Bífida Quística , Embarazo , Femenino , Humanos , Espina Bífida Quística/diagnóstico por imagen , Espina Bífida Quística/cirugía , Estudios Retrospectivos , Edad Gestacional , Encéfalo , Imagen por Resonancia Magnética
2.
Eur J Neurol ; 29(10): 3117-3123, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35763378

RESUMEN

BACKGROUND AND PURPOSE: Enterovirus infections pose a serious threat for patients with humoral deficiencies and may be lethal, whilst the efficacy of proposed treatment options such as corticosteroids, intravenous immunoglobulins and fluoxetine remains debated. METHODS: Viral clearance was investigated in a patient with rituximab-induced B-cell depletion and chronic echovirus 13 (E13) meningoencephalitis/myofasciitis in response to intravenous immunoglobulins and fluoxetine using sequential semi-quantitative E13 viral load measurements by real-time reverse transcription polymerase chain reaction. Fluoxetine concentrations in plasma and cerebrospinal fluid were determined by liquid chromatography mass spectrometry. RESULTS: Intravenous immunoglobulins appeared ineffective in this case of E13 infection, whereas virus clearance in cerebrospinal fluid was obtained after 167 days of oral fluoxetine. Since treatment with corticosteroids resulted in a flare of symptoms, rechallenge with viral load measurements was not attempted. CONCLUSION: In this report of a patient with rituximab-associated chronic echovirus 13 meningoencephalitis, viral clearance in response to single treatment options is assessed for the first time. Our observations further support the in vivo efficacy of fluoxetine against enteroviral infections. More research is needed to establish its efficacy in different enterovirus strains.


Asunto(s)
Infecciones por Echovirus , Infecciones por Enterovirus , Meningitis Aséptica , Meningoencefalitis , Miositis , Antivirales , Infecciones por Echovirus/líquido cefalorraquídeo , Enterovirus Humano B , Fluoxetina/uso terapéutico , Humanos , Inmunoglobulinas Intravenosas/uso terapéutico , Meningoencefalitis/líquido cefalorraquídeo , Meningoencefalitis/tratamiento farmacológico , Rituximab/uso terapéutico
3.
Neuroophthalmology ; 46(3): 171-177, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35574162

RESUMEN

Two cases of optic neuropathy due to superficial siderosis (SS) are reported in two patients, aged 29 and 38 years, operated for intracranial neoplasms, the first one with a desmoplasic infantile ganglioglioma excised in 1991, and the other one with a pilocytic astrocytoma, operated on in 1997, 1998 and 2016. Both patients presented with progressive loss of visual acuity, as a result of bilateral optic nerve atrophy, as well as unsteadiness, ataxic gait and hearing loss. Magnetic resonance imaging (MRI) of the brain and spine, including gradient echo (GRE) T2-weighted acquisitions, revealed thin optic nerves and strong hypointensity with susceptibility artefacts corresponding to haemosiderin deposits within the meningeal layers of the spine, the infra- and supratentorial spaces of the brain and the peri-optic sheaths in both patients. The cerebrospinal fluid (CSF) was macroscopically haemorrhagic in one patient, who underwent a dynamic myelography, which failed to reveal any trans-dural CSF leakage. Neuro-ophthalmological symptoms due to SS, such as visual acuity loss, have been scarcely reported. MRI using GRE T2-weighted sequences highlighting the presence of haemosiderin deposits plays a key role in the diagnosis of this condition. Treatment should aim at preventing haemosiderin deposition by treating the cause of the subarachnoid bleeding.

4.
Neuroradiology ; 63(5): 817-820, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33410947

RESUMEN

A 39-year-old woman presented with sudden onset of double vision, right upper eyelid swelling and ptosis, and orbital pain. Imaging revealed an irregular mass of the upper right orbit with central non-enhancing areas. Upon inquiry, the patient recalled an intraorbital trauma with a crayon in her childhood, 35 years ago. Via translid anterior orbitotomy, remnants of a blue crayon embedded in an orbital fat mass were removed. Histopathology showed scavenger reaction of macrophages and sclerosis. Energy-dispersive X-ray spectroscopy revealed the presence of silicate particles. Repeated courses of corticosteroids were given. The patient deteriorated with reduced vision and frozen globe owing to severe orbital fibrosis of the entire orbit.


Asunto(s)
Órbita , Enfermedades Orbitales , Adulto , Niño , Femenino , Fibrosis , Humanos , Inflamación/diagnóstico por imagen , Órbita/diagnóstico por imagen , Órbita/patología , Enfermedades Orbitales/diagnóstico por imagen , Enfermedades Orbitales/etiología , Esclerosis/patología
5.
Neuroradiology ; 63(10): 1721-1734, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-33934181

RESUMEN

PURPOSE: A retrospective study was performed to study the effect of fetal surgery on brain development measured by MRI in fetuses with myelomeningocele (MMC). METHODS: MRI scans of 12 MMC fetuses before and after surgery were compared to 24 age-matched controls without central nervous system abnormalities. An automated super-resolution reconstruction technique generated isotropic brain volumes to mitigate 2D MRI fetal motion artefact. Unmyelinated white matter, cerebellum and ventricles were automatically segmented, and cerebral volume, shape and cortical folding were thereafter quantified. Biometric measures were calculated for cerebellar herniation level (CHL), clivus-supraocciput angle (CSO), transverse cerebellar diameter (TCD) and ventricular width (VW). Shape index (SI), a mathematical marker of gyrification, was derived. We compared cerebral volume, surface area and SI before and after MMC fetal surgery versus controls. We additionally identified any relationship between these outcomes and biometric measurements. RESULTS: MMC ventricular volume/week (mm3/week) increased after fetal surgery (median: 3699, interquartile range (IQR): 1651-5395) compared to controls (median: 648, IQR: 371-896); P = 0.015. The MMC SI is higher pre-operatively in all cerebral lobes in comparison to that in controls. Change in SI/week in MMC fetuses was higher in the left temporal lobe (median: 0.039, IQR: 0.021-0.054), left parietal lobe (median: 0.032, IQR: 0.023-0.039) and right occipital lobe (median: 0.027, IQR: 0.019-0.040) versus controls (P = 0.002 to 0.005). Ventricular volume (mm3) and VW (mm) (r = 0.64), cerebellar volume and TCD (r = 0.56) were moderately correlated. CONCLUSIONS: Following fetal myelomeningocele repair, brain volume, shape and SI were significantly different from normal in most cerebral layers. Morphological brain changes after fetal surgery are not limited to hindbrain herniation reversal. These findings may have neurocognitive outcome implications and require further evaluation.


Asunto(s)
Meningomielocele , Disrafia Espinal , Encéfalo/diagnóstico por imagen , Encéfalo/cirugía , Feto , Humanos , Imagen por Resonancia Magnética , Meningomielocele/diagnóstico por imagen , Meningomielocele/cirugía , Estudios Retrospectivos
6.
J Cutan Pathol ; 48(12): 1497-1503, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34255877

RESUMEN

Congenital melanocytic nevus syndrome (CMNS) is a rare condition characterized by pigmented skin lesions that are usually present at birth and are associated with an increased risk of neurological abnormalities and malignant melanoma. It mostly results from a post-zygotic NRAS mutation of neural-derived crest cells, leading to uncontrolled cell growth. Because of the increased knowledge of the genetics underlying CMNS, targeted therapy becomes a promising treatment option. We present a case of CMNS in a newborn. Physical examination at birth showed a giant congenital melanocytic nevus, extending from the occipital to the lower lumbar region. A magnetic resonance imaging scan revealed multiple cerebral and cerebellar parenchymal lesions. Genetic analysis of the cutaneous lesions showed the presence of an NRAS Q61R mutation. The patient was treated with dermabrasion to reduce the color intensity of the nevus. However, this was complicated by recurrent wound infections and laborious wound healing. At the age of 1 year, the patient had an age-appropriate psychomotor development, without neurological deficits.


Asunto(s)
Nevo Pigmentado/patología , Neoplasias Cutáneas/patología , Dermabrasión/métodos , GTP Fosfohidrolasas/genética , Humanos , Recién Nacido , Masculino , Proteínas de la Membrana/genética , Mutación , Nevo Pigmentado/genética , Nevo Pigmentado/cirugía , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/cirugía
7.
Neuroradiology ; 62(11): 1361-1369, 2020 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-32500276

RESUMEN

PURPOSE: The aim of this study is to compare a qualitative and a quantitative assessment of brain diffusion-weighted imaging (DWI) in predicting outcome of comatose patients after cardiac arrest (CA). METHODS: Two observers used a scoring template to analyze the DWI of 75 patients. A total of 13 regions were scored from 0 to 3 (0 = normal, 1 = probably normal, 2 = probably abnormal, 3 = definitely abnormal). The total cerebral cortex (TCC), the total deep grey nuclei (TDGN), the total brain stem, the total cerebellum, and the total brain score were calculated. Intra- and inter-observer variability were tested. The mean whole brain apparent diffusion coefficient (ADC) values and percentage of voxels below a specific ADC value cut-off were calculated. The data were correlated with clinical outcome (cerebral performance category score after 180 days, dichotomized in a score 1-2 with favorable outcome and score 3-5 with unfavorable outcome) using ROC analysis. RESULTS: Intra-observer variability was excellent for the TCC score (ICC 0.95 and 0.86) and the TDGN score (ICC 0.89 and 0.75). Inter-observer variability was good to excellent for total cerebral cortex score and total deep grey nuclei score in both the first (ICC 0.78 and 0.69) and third (ICC 0.86 and 0.83) image assessment. TCC and TDGN score show the best correlation with clinical outcome (highest AUC values 0.87 and 0.87). Quantitative parameters did not show good correlation with clinical outcome (AUC values 0.57 and 0.60). CONCLUSION: A qualitative assessment of brain DWI using a scoring template provides useful data regarding patient outcome while quantitative data appeared less reliable.


Asunto(s)
Coma/diagnóstico por imagen , Imagen de Difusión por Resonancia Magnética/métodos , Paro Cardíaco , Anciano , Bélgica , Femenino , Humanos , Masculino , Persona de Mediana Edad , Examen Neurológico , Pronóstico , Estudios Prospectivos , Sensibilidad y Especificidad , Sobrevivientes
8.
Eur Heart J ; 40(22): 1804-1814, 2019 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-30895296

RESUMEN

AIMS: During the first 6-12 h of intensive care unit (ICU) stay, post-cardiac arrest (CA) patients treated with a mean arterial pressure (MAP) 65 mmHg target experience a drop of the cerebral oxygenation that may cause additional cerebral damage. Therefore, we investigated whether an early goal directed haemodynamic optimization strategy (EGDHO) (MAP 85-100 mmHg, SVO2 65-75%) is safe and could improve cerebral oxygenation, reduce anoxic brain damage, and improve outcome when compared with a MAP 65 mmHg strategy. METHODS AND RESULTS: A total of 112 out-of-hospital CA patients were randomly assigned to EGDHO or MAP 65 mmHg strategies during the first 36 h of ICU stay. The primary outcome was the extent of anoxic brain damage as quantified by the percentage of voxels below an apparent diffusion coefficient (ADC) score of 650.10-6 mm2/s on diffusion weighted magnetic resonance imaging (at day 5 ± 2 post-CA). Main secondary outcome was favourable neurological outcome (CPC score 1-2) at 180 days. In patients assigned to EGDHO, MAP (P < 0.001), and cerebral oxygenation during the first 12 h of ICU stay (P = 0.04) were higher. However, the percentage of voxels below an ADC score of 650.10-6 mm2/s did not differ between both groups [16% vs. 12%, odds ratio 1.37, 95% confidence interval (CI) 0.95-0.98; P = 0.09]. Also, the number of patients with favourable neurological outcome at 180 days was similar (40% vs. 38%, odds ratio 0.98, 95% CI 0.41-2.33; P = 0.96). The number of serious adverse events was lower in patients assigned to EGDHO (P = 0.02). CONCLUSION: Targeting a higher MAP in post-CA patients was safe and improved cerebral oxygenation but did not improve the extent of anoxic brain damage or neurological outcome.


Asunto(s)
Hemodinámica/fisiología , Hipoxia Encefálica/prevención & control , Neuroprotección/fisiología , Paro Cardíaco Extrahospitalario/terapia , Anciano , Encéfalo/irrigación sanguínea , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Coma/etiología , Coma/fisiopatología , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Hipoxia Encefálica/etiología , Masculino , Persona de Mediana Edad , Paro Cardíaco Extrahospitalario/complicaciones , Oxígeno/sangre , Oxígeno/metabolismo , Resultado del Tratamiento , Troponina/sangre
9.
BMC Pediatr ; 18(1): 250, 2018 07 31.
Artículo en Inglés | MEDLINE | ID: mdl-30064396

RESUMEN

BACKGROUND: Upper limb (UL) deficits in children with unilateral cerebral palsy (uCP) have traditionally been targeted with motor execution treatment models, such as modified Constraint-Induced Movement Therapy (mCIMT). However, new approaches based on a neurophysiological model such as Action-Observation Training (AOT) may provide new opportunities for enhanced motor learning. The aim of this study is to describe a randomised controlled trial (RCT) protocol investigating the effects of an intensive treatment model, combining mCIMT and AOT compared to mCIMT alone on UL function in children with uCP. Additionally, the role of neurological factors as potential biomarkers of treatment response will be analysed. METHODS: An evaluator-blinded RCT will be conducted in 42 children aged between 6 and 12 years. Before randomization, children will be stratified according to their House Functional Classification Scale, age and type of corticospinal tract wiring. A 2-week day-camp will be set up in which children receive intensive mCIMT therapy for 6 hours a day on 9 out of 11 consecutive days (54 h) including AOT or control condition (15 h). During AOT, these children watch video sequences showing goal-directed actions and subsequently execute the observed actions with the more impaired UL. The control group performs the same actions after watching computer games without human motion. The primary outcome measure will be the Assisting Hand Assessment. Secondary outcomes comprise clinical assessments across body function, activity and participation level of the International Classification of Function, Disability and Health. Furthermore, to quantitatively evaluate UL movement patterns, a three-dimensional motion analysis will be conducted. UL function will be assessed at baseline, immediately before and after intervention and at 6 months follow up. Brain imaging comprising structural and functional connectivity measures as well as Transcranial Magnetic Stimulation (TMS) to evaluate corticospinal tract wiring will be acquired before the intervention. DISCUSSION: This paper describes the methodology of an RCT with two main objectives: (1) to evaluate the added value of AOT to mCIMT on UL outcome in children with uCP and (2) to investigate the role of neurological factors as potential biomarkers of treatment response. TRIAL REGISTRATION: NCT03256357 registered on 21st August 2017 (retrospectively registered).


Asunto(s)
Parálisis Cerebral/rehabilitación , Terapia por Ejercicio/métodos , Estimulación Magnética Transcraneal , Extremidad Superior/fisiopatología , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Parálisis Cerebral/fisiopatología , Niño , Terapia Combinada , Humanos , Proyectos de Investigación , Método Simple Ciego , Grabación de Cinta de Video
11.
Eur Spine J ; 26(4): 1191-1198, 2017 04.
Artículo en Inglés | MEDLINE | ID: mdl-27904963

RESUMEN

PURPOSE: Cervical arthroplasty is being used as an alternative for cervical fusion, but long-term follow-up results have rarely been reported. In this paper, we present 10-year follow-up results after implantation of the Bryan Cervical Disc Prosthesis in a single center. METHODS: 89 patients underwent implantation of a single-level Bryan Cervical Disc Prosthesis to treat radiculopathy and/or myelopathy. Clinical (Neurological Success, Neck Disability Index (NDI), Neck- and Arm-Pain, and SF-36) and radiological follow-up was prospectively organized up to 10 years after surgery. Adverse events and second surgeries were recorded and evaluated. RESULTS: Ten-year follow-up data were available for 72 (81%) patients. Maintenance or improvement of the neurological state was seen in 89% of patients after 10-year follow-up. SF-36 PCS scores improved significantly at all follow-up points. SF-36 MCS improvement was significant at 4 and 6 year, but not at 8- and 10-year follow-up. Significant improvement for NDI, and Neck- and Arm-Pain scores was found for the subgroup of patients in whom these data were available. Mean angular motion of the prosthesis at 10-year follow-up was 8.6°. Mobility of the device, defined as >2° of angular motion, was reached in 81% of patients. During the study period, 21 patients (24%) developed new or recurrent radiculopathy or myelopathy, the majority of these being treated conservatively. Seven patients (8%) required 8 additional spine surgeries to treat persistent or recurrent symptoms. Of these, 2 patients (2%) were reoperated at the index level and at 5 (6%) an adjacent level. CONCLUSION: In this study, favorable long-term clinical outcome after implantation of the Bryan Cervical Disc Prosthesis was seen, with the majority of prostheses remaining mobile after 10-year follow-up. However, still 6% of patients required adjacent level surgery.


Asunto(s)
Vértebras Cervicales/cirugía , Disco Intervertebral/cirugía , Procedimientos Ortopédicos , Implantación de Prótesis , Estudios de Seguimiento , Humanos , Procedimientos Ortopédicos/instrumentación , Procedimientos Ortopédicos/métodos , Implantación de Prótesis/instrumentación , Implantación de Prótesis/métodos
12.
Clin Anat ; 30(4): 543-549, 2017 May.
Artículo en Inglés | MEDLINE | ID: mdl-28247932

RESUMEN

Hypertrophic olivary degeneration (HOD) following a lesion of the dentato-rubro-olivary pathway (DROP) is a well-known imaging finding and has extensively been described in the recent literature. We reviewed our patients with HOD as a result of a lesion of the DROP in order to analyze the disruption of the DROP and the resulting HOD in comparison with the literature. We observed unusual imaging findings in four patients. In two patients it concerned new observations related to the timing and imaging appearances of HOD. HOD became only visible 6 years after a lesion in the red nucleus in one patient and a cystic degeneration of the olivary nucleus was seen 3 years after the HOD in a second patient. In two patients we found HOD that could only be explained by the existence of an afferent feedback loop between the dentate nucleus and the inferior olivary nucleus and by the knowledge that these fibers run through the ipsilateral olivary nucleus before ending in the contralateral olivary nucleus. In one of these patients the lesion was located in the inferior cerebellar peduncle. In the other patient the lesion was located on the midline in the medulla oblongata. The imaging findings in these patients reveal new observations in the stages of imaging appearances in HOD and shed light on the forgotten dentato-olivary afferent feedback loop of the DROP. Clin. Anat. 30:543-549, 2017. © 2017 Wiley Periodicals, Inc.


Asunto(s)
Imagen por Resonancia Magnética/métodos , Enfermedades Neurodegenerativas/diagnóstico por imagen , Núcleo Olivar/patología , Niño , Femenino , Humanos , Hipertrofia/patología , Masculino , Persona de Mediana Edad
13.
Neuroimage ; 134: 281-294, 2016 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-27039700

RESUMEN

A concern for researchers planning multisite studies is that scanner and T1-weighted sequence-related biases on regional volumes could overshadow true effects, especially for studies with a heterogeneous set of scanners and sequences. Current approaches attempt to harmonize data by standardizing hardware, pulse sequences, and protocols, or by calibrating across sites using phantom-based corrections to ensure the same raw image intensities. We propose to avoid harmonization and phantom-based correction entirely. We hypothesized that the bias of estimated regional volumes is scaled between sites due to the contrast and gradient distortion differences between scanners and sequences. Given this assumption, we provide a new statistical framework and derive a power equation to define inclusion criteria for a set of sites based on the variability of their scaling factors. We estimated the scaling factors of 20 scanners with heterogeneous hardware and sequence parameters by scanning a single set of 12 subjects at sites across the United States and Europe. Regional volumes and their scaling factors were estimated for each site using Freesurfer's segmentation algorithm and ordinary least squares, respectively. The scaling factors were validated by comparing the theoretical and simulated power curves, performing a leave-one-out calibration of regional volumes, and evaluating the absolute agreement of all regional volumes between sites before and after calibration. Using our derived power equation, we were able to define the conditions under which harmonization is not necessary to achieve 80% power. This approach can inform choice of processing pipelines and outcome metrics for multisite studies based on scaling factor variability across sites, enabling collaboration between clinical and research institutions.


Asunto(s)
Artefactos , Encéfalo/anatomía & histología , Interpretación de Imagen Asistida por Computador/instrumentación , Interpretación de Imagen Asistida por Computador/métodos , Imagen por Resonancia Magnética/instrumentación , Imagen por Resonancia Magnética/métodos , Modelos Estadísticos , Algoritmos , Simulación por Computador , Diseño de Equipo , Análisis de Falla de Equipo , Europa (Continente) , Humanos , Aumento de la Imagen/instrumentación , Aumento de la Imagen/métodos , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Estados Unidos
14.
Hum Mol Genet ; 22(2): 391-7, 2013 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-23065703

RESUMEN

Mutations in COL4A1 have been identified in families with hereditary small vessel disease of the brain presumably due to a dominant-negative mechanism. Here, we report on two novel mutations in COL4A1 in two families with porencephaly, intracerebral hemorrhage and severe white matter disease caused by haploinsufficiency. Two families with various clinical presentations of cerebral microangiopathy and autosomal dominant inheritance were examined. Clinical, neuroradiological and genetic investigations were performed. Electron microscopy of the skin was also performed. In one of the families, sequence analysis revealed a one base deletion, c.2085del, leading to a frameshift and a premature stopcodon, p.(Gly696fs). In the other family, a splice site mutation was identified, c.2194-1G>A, which most likely leads to skipping of an exon with a frameshift and premature termination as a result. In fibroblasts of affected individuals from both the families, nonsense-mediated decay (NMD) of the mutant COL4A1 messenger RNAs (mRNAs) and a clear reduction of COL4A1 protein expression were demonstrated, indicating haploinsufficiency of COL4A1. Moreover, thickening of the capillary basement membrane in the skin was documented, similar to reports in patients with COL4A1 missense mutations. These findings suggest haploinsufficiency, a different mechanism from the commonly assumed dominant-negative effect, for COL4A1 mutations as a cause of (antenatal) intracerebral hemorrhage and white matter disease.


Asunto(s)
Enfermedades de los Pequeños Vasos Cerebrales/genética , Colágeno Tipo IV/genética , Haploinsuficiencia , Mutación , Adulto , Anciano , Secuencia de Bases , Membrana Basal/metabolismo , Encéfalo/patología , Enfermedades de los Pequeños Vasos Cerebrales/diagnóstico , Femenino , Fibroblastos/metabolismo , Fibroblastos/patología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Linaje , Adulto Joven
15.
Eur Radiol ; 30(10): 5599-5601, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32377811
16.
Cureus ; 16(5): e60427, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38882976

RESUMEN

This case report presents a unique presentation of an intradiploic epidermoid cyst (IDEC) in a 55-year-old female. She presented with acute cerebellar symptoms triggered by a Valsalva maneuver. IDECs are a rare type of intracranial epidermoid cysts. They are benign and have a slow growth pattern that translates into progressively developing symptoms instead of acute symptoms. Symptoms include local deformities, focal neurologic deficits, and pain. This patient developed acute cerebellar symptoms due to erosion of the mastoid bone that created a pathway between the eustachian tube and the intracranial space via the mastoid air cells. Consequently, tension pneumocephalus emerged via a ball-valve effect that caused a significant mass effect in the posterior fossa. Surgical resection of the IDEC and closing of the mastoid air cells resulted in symptom relief by restoring the integrity of the intracranial-extracranial barrier. This case highlights that a higher level of vigilance is warranted for an IDEC in the proximity of aerated bone structures, such as the mastoid air cells and the paranasal sinuses, and that a more proactive approach is advocated.

17.
J Clin Invest ; 134(4)2024 Jan 04.
Artículo en Inglés | MEDLINE | ID: mdl-38175705

RESUMEN

Mutations in the N-terminal WD40 domain of coatomer protein complex subunit α (COPA) cause a type I interferonopathy, typically characterized by alveolar hemorrhage, arthritis, and nephritis. We described 3 heterozygous mutations in the C-terminal domain (CTD) of COPA (p.C1013S, p.R1058C, and p.R1142X) in 6 children from 3 unrelated families with a similar syndrome of autoinflammation and autoimmunity. We showed that these CTD COPA mutations disrupt the integrity and the function of coat protein complex I (COPI). In COPAR1142X and COPAR1058C fibroblasts, we demonstrated that COPI dysfunction causes both an anterograde ER-to-Golgi and a retrograde Golgi-to-ER trafficking defect. The disturbed intracellular trafficking resulted in a cGAS/STING-dependent upregulation of the type I IFN signaling in patients and patient-derived cell lines, albeit through a distinct molecular mechanism in comparison with mutations in the WD40 domain of COPA. We showed that CTD COPA mutations induce an activation of ER stress and NF-κB signaling in patient-derived primary cell lines. These results demonstrate the importance of the integrity of the CTD of COPA for COPI function and homeostatic intracellular trafficking, essential to ER homeostasis. CTD COPA mutations result in disease by increased ER stress, disturbed intracellular transport, and increased proinflammatory signaling.


Asunto(s)
Proteína Coat de Complejo I , Proteína Coatómero , Niño , Humanos , Proteína Coatómero/genética , Proteína Coat de Complejo I/genética , Proteína Coat de Complejo I/metabolismo , Mutación , Síndrome , Aparato de Golgi/genética , Aparato de Golgi/metabolismo
19.
J Comput Assist Tomogr ; 37(2): 279-81, 2013.
Artículo en Inglés | MEDLINE | ID: mdl-23493219

RESUMEN

We present a case in which mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome mimicked the clinical and radiological signs of herpes simplex encephalitis. In a patient with subacute encephalopathy, on computed tomography and magnetic resonance imaging, lesions were present in both temporal lobes extending to both insular regions with sparing of the lentiform nuclei and in both posterior straight and cingulate gyri. Final diagnosis of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes syndrome was based on biochemical investigations on cerebrospinal fluid, electromyogram, muscle biopsy, and genetic analysis. On diffusion-weighted imaging, diffusion restriction was present in some parts of the lesions but not throughout the entire lesions. We suggest that this could be an important sign in the differential diagnosis with herpes simplex encephalitis.


Asunto(s)
Diagnóstico por Imagen , Síndrome MELAS/diagnóstico , Adulto , Biopsia , Diagnóstico Diferencial , Electroencefalografía , Electromiografía , Encefalitis por Herpes Simple/diagnóstico , Humanos , Masculino , Reacción en Cadena de la Polimerasa
20.
World Neurosurg ; 179: e212-e221, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37611801

RESUMEN

OBJECTIVE: The NeVa stent retriever is a newly designed mechanical thrombectomy device for the treatment of acute ischemic stroke caused by large vessel occlusion. We investigate the procedural characteristics and patients' clinical outcomes at discharge and at 90 days of follow-up. METHODS: We retrospectively reviewed a cohort of 75 patients (median age, 74 years) treated with the NeVa device for acute large vessel occlusion stroke. Per pass modified Treatment in Cerebral Infarction (mTICI) scores, procedural complications, and clinical outcome parameters including the National Institutes of Health Stroke Scale (NIHSS) score, modified Rankin Scale (mRS) score, and mortality were analyzed, based on patients' electronic medical records. RESULTS: Complete first pass effect was observed in 24 patients (32%). Vasospasm, repeated re-thrombosis, failure to advance the NeVa device through the microcatheter, and symptomatic intracranial hemorrhage were observed in 2, 1, 1, and 2 patient(s) respectively. The rate of complete (mTICI 2c-3) reperfusion was achieved in 61 patients (81.33%), with a median number of 2 passes (1-3). Median NIHSS score on admission, after 24 hours, and after 5-10 days or at discharge was 19 (15-23), 11 (4-19), and 3 (2-13.5), respectively. The number of patients with a functional mRS score (0-2) at 90 days follow-up was 29 (39%). CONCLUSIONS: Endovascular stroke management with use of the NeVa-Vesalio stent retriever may be associated with a 90-day functional mRS score in nearly 40% of treated patients.


Asunto(s)
Isquemia Encefálica , Procedimientos Endovasculares , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Anciano , Estudios Retrospectivos , Isquemia Encefálica/diagnóstico por imagen , Isquemia Encefálica/cirugía , Isquemia Encefálica/complicaciones , Accidente Cerebrovascular Isquémico/etiología , Trombectomía , Resultado del Tratamiento , Accidente Cerebrovascular/etiología , Infarto Cerebral/etiología , Stents/efectos adversos
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