Novel NDUFA13 Mutations Associated with OXPHOS Deficiency and Leigh Syndrome: A Second Family Report.

Leigh syndrome (LS) usually presents as an early onset mitochondrial encephalopathy characterized by bilateral symmetric lesions in the basal ganglia and cerebral stem. More than 75 genes have been associated with this condition, including genes involved in the biogenesis of mitochondrial complex I (CI). In this study, we used a next-generation sequencing (NGS) panel to identify two novel biallelic variants in the NADH:ubiquinone oxidoreductase subunit A13 (NDUFA13) gene in a patient with isolated CI deficiency in skeletal muscle. Our patient, who represents the second family report with mutations in the CI NDUFA13 subunit, presented with LS lesions in brain magnetic resonance imaging, mild hypertrophic cardiomyopathy, and progressive spastic tetraparesis. This phenotype manifestation is different from that previously described in the first NDUFA13 family, which was predominantly characterized by neurosensorial symptoms. Both in silico pathogenicity predictions and oxidative phosphorylation (OXPHOS) functional findings in patient's skin fibroblasts (delayed cell growth, isolated CI enzyme defect, decreased basal and maximal oxygen consumption and as well as ATP production, together with markedly diminished levels of the NDUFA13 protein, CI, and respirasomes) suggest that these novel variants in the NDUFA13 gene are the underlying cause of the CI defect, expanding the genetic heterogeneity of LS.

Anterior cingulate and medial prefrontal cortex response to systematically controlled tonal dissonance during passive music listening.

Several studies have attempted to investigate how the brain codes emotional value when processing music of contrasting levels of dissonance; however, the lack of control over specific musical structural characteristics (i.e., dynamics, rhythm, melodic contour or instrumental timbre), which are known to affect perceived dissonance, rendered results difficult to interpret. To account for this, we used functional imaging with an optimized control of the musical structure to obtain a finer characterization of brain activity in response to tonal dissonance. Behavioral findings supported previous evidence for an association between increased dissonance and negative emotion. Results further demonstrated that the manipulation of tonal dissonance through systematically controlled changes in interval content elicited contrasting valence ratings but no significant effects on either arousal or potency. Neuroscientific findings showed an engagement of the left medial prefrontal cortex (mPFC) and the left rostral anterior cingulate cortex (ACC) while participants listened to dissonant compared to consonant music, converging with studies that have proposed a core role of these regions during conflict monitoring (detection and resolution), and in the appraisal of negative emotion and fear-related information. Both the left and right primary auditory cortices showed stronger functional connectivity with the ACC during the dissonant portion of the task, implying a demand for greater information integration when processing negatively valenced musical stimuli. This study demonstrated that the systematic control of musical dissonance could be applied to isolate valence from the arousal dimension, facilitating a novel access to the neural representation of negative emotion.

Novel ATAD3A recessive mutation associated to fatal cerebellar hypoplasia with multiorgan involvement and mitochondrial structural abnormalities.

Lethal neonatal encephalopathies are heterogeneous congenital disorders that can be caused by mitochondrial dysfunction. Biallelic large deletions in the contiguous ATAD3B and ATAD3A genes, encoding mitochondrial inner membrane ATPases of unknown function, as well as compound heterozygous nonsense and missense mutations in the ATAD3A gene have been recently associated with fatal neonatal cerebellar hypoplasia. In this work, whole exome sequencing (WES) identified the novel homozygous variant c.1217 T > G in ATAD3A, predicting a p.(Leu406Arg) substitution, in four siblings from a consanguineous family presenting with fatal neonatal cerebellar hypoplasia, seizures, axial hypotonia, hypertrophic cardiomyopathy, hepatomegaly, congenital cataract, and dysmorphic facies. Biochemical phenotypes of the patients included hyperlactatemia and hypocholesterolemia. Healthy siblings and parents were heterozygous for this variant, which is predicted to introduce a polar chain within the catalytic domain of ATAD3A that shortens its beta-sheet structure, presumably affecting protein stability. Accordingly, patient's fibroblasts with the homozygous variant displayed a specific reduction in ATAD3A protein levels associated with profound ultrastructural alterations of mitochondrial cristae and morphology. Our findings exclude the causative role of ATAD3B on this severe phenotype, expand the phenotypical spectrum of ATAD3A pathogenic variants and emphasize the vital role of ATAD3A in mitochondrial biogenesis.

Neural mechanisms underlying valence inferences to sound: The role of the right angular gyrus.

We frequently infer others' intentions based on non-verbal auditory cues. Although the brain underpinnings of social cognition have been extensively studied, no empirical work has yet examined the impact of musical structure manipulation on the neural processing of emotional valence during mental state inferences. We used a novel sound-based theory-of-mind paradigm in which participants categorized stimuli of different sensory dissonance level in terms of positive/negative valence. Whilst consistent with previous studies which propose facilitated encoding of consonances, our results demonstrated that distinct levels of consonance/dissonance elicited differential influences on the right angular gyrus, an area implicated in mental state attribution and attention reorienting processes. Functional and effective connectivity analyses further showed that consonances modulated a specific inhibitory interaction from associative memory to mental state attribution substrates. Following evidence suggesting that individuals with autism may process social affective cues differently, we assessed the relationship between participants' task performance and self-reported autistic traits in clinically typical adults. Higher scores on the social cognition scales of the AQ were associated with deficits in recognising positive valence in consonant sound cues. These findings are discussed with respect to Bayesian perspectives on autistic perception, which highlight a functional failure to optimize precision in relation to prior beliefs.

Neurovascular study of the trigeminal nerve at 3 t MRI.

This study aimed to show a novel visualization method to investigate neurovascular compression of the trigeminal nerve (TN) using a volume-rendering fusion imaging technique of 3D fast imaging employing steady-state acquisition (3D FIESTA) and coregistered 3D time of flight MR angiography (3D TOF MRA) sequences, which we called "neurovascular study of the trigeminal nerve". We prospectively studied 30 patients with unilateral trigeminal neuralgia (TN) and 50 subjects without symptoms of TN (control group), on a 3 Tesla scanner. All patients were assessed using 3D FIESTA and 3D TOF MRA sequences centered on the pons, as well as a standard brain protocol including axial T1, T2, FLAIR and GRE sequences to exclude other pathologies that could cause TN. Post-contrast T1-weighted sequences were also performed. All cases showing arterial imprinting on the trigeminal nerve (n = 11) were identified on the ipsilateral side of the pain. No significant relationship was found between the presence of an artery in contact with the trigeminal nerve and TN. Eight cases were found showing arterial contact on the ipsilateral side of the pain and five cases of arterial contact on the contralateral side. The fusion imaging technique of 3D FIESTA and 3D TOF MRA sequences, combining the high anatomical detail provided by the 3D FIESTA sequence with the 3D TOF MRA sequence and its capacity to depict arterial structures, results in a tool that enables quick and efficient visualization and assessment of the relationship between the trigeminal nerve and the neighboring vascular structures.

Cystic meningioma simulating arachnoid cyst: report of an unusual case.

The purpose of this paper is to show an unusual case of meningioma simulating arachnoid cyst on CT scan and MRI, diagnosed in a 63-year-old woman evaluated for headache and vision disorders. The meningioma shown is predominantly cystic with a small mural nodule enhancing after gadolinium and exhibiting diffusion restriction. Cystic portion of the tumor is hypodense on CT, and evidences fluid signal intensity on T1- and T2-weighted MR imaging.

Susceptibility-weighted angiography of intracranial blood products and calcifications compared to gradient echo sequence.

This study evaluated the sensitivity of susceptibility-weighted angiography (SWAN) compared with gradient echo (GRE) sequence in the depiction of haemorrhagic and calcium lesions by virtue of correlation analysis between the number, area and contrast index. The study included 21 patients (15 women, 6 men; age range 18 to 80 years) in whom intracranial haemorrhage or calcifications were previously diagnosed with CT and/or MR. GRE and SWAN sequences were performed as part of a conventional Brain MR study using a 3T scanner. Pathologic findings were: cavernoma (n=8), chronic intraparenchymal haemorrhage (n=5), petechial bleeding (n=3), parenchymal calcifications (n=2), sequelae of haemorrhagic contusion focus (n=1), post-surgical glioma (n=1) and venous angioma (n=1). In eight patients, more lesions were found in the SWAN sequence than in GRE. In the measurement of the largest area, in all cases the measured area was larger in the SWAN sequence than in GRE. The SWAN sequence was reported to have shown higher contrast between the lesion and the healthy white matter than in GRE. The SWAN sequence is more sensitive than GRE in the identification of cerebral haemorrhage and calcifications. The SWAN sequence also obtained significantly larger images than with GRE, and a higher contrast difference between the lesion and the healthy parenchyma.

Neurotuberculosis. Hallazgos intracraneanos en RM / Neurotuberculosis. Intracranial MRI findings

Objetivos. Mostrar nuestra casuística de pacientes con diagnóstico de tuberculosis intracraneana y describir los diferentes tipos de lesiones documentadas en Resonancia Magnética (RM) que caracterizan a esta entidad. Materiales y Métodos. Para el presente trabajo fueron seleccionados, de forma retrospectiva, 20 pacientes con hallazgos positivos de tuberculosis intracraneana. Doce eran de sexo masculino y 8 de sexo femenino, conun rango etario de 8 meses a 49 años de edad (edad media: 21 años). El diagnóstico clínico fue realizado con punción lumbar y cultivo de LCR. Once pacientes presentaron serología positiva para VIH. Las RM fueron realizadas en resonadores de 0.5T y 1.5T, complementadas en dos casos con Tomografía Computada (TC) de cerebro. A dos pacientes se les realizó difusión (DWI) y a un paciente espectroscopía. Resultados. Del total de pacientes (n=20), 14 presentaron compromiso subaracnoideo en la convexidad y 13 compromiso subaracnoideo cisternal basal (afectación leptomeníngea). En 13 se observaron tuberculomas y 11 presentaron angeítis de grandes vasos; mientras que 7 tuvieron angeítis de pequeños vasos, 7 hidrocefalia, 6 infartos parenquimatosos y 1 afectación paquimeníngea. Quince pacientes tenían lesiones combinadas.Conclusión. La localización más frecuente de neurotuberculosis en esta serie fue meníngea con compromiso leptomeníngeo (14 pacientes con afectación subaracnoidea, seguido de afectación cisternal en 13 pacientes) y sólo en un caso fue paquimeníngea. La manifestación parenquimatosa más frecuente fue el tuberculoma (granulomas tuberculosos) con 13 casos. De estos, 5 presentaron un patrón miliar y sólo uno comportamiento pseudotumoral...

Neurotuberculosis: Hallazgos intracraneanos en RM / Neurotuberculosis: Intracranial MRI findings

Objetivos. Mostrar nuestra casuística de pacientes con diagnóstico de tuberculosis intracraneana y describir los diferentes tipos de lesiones documentadas en Resonancia Magnética (RM) que caracterizan a esta entidad. Materiales y Métodos. Para el presente trabajo fueron seleccionados, de forma retrospectiva, 20 pacientes con hallazgos positivos de tuberculosis intracraneana. Doce eran de sexo masculino y 8 de sexo femenino, con un rango etario de 8 meses a 49 años de edad (edad media: 21 años). El diagnóstico clínico fue realizado con punción lumbar y cultivo de LCR. Once pacientes presentaron serología positiva para VIH. Las RM fueron realizadas en resonadores de 0.5T y 1.5T, complementadas en dos casos con Tomografía Computada (TC) de cerebro. A dos pacientes se les realizó difusión (DWI) y a un paciente espectroscopía. Resultados. Del total de pacientes (n=20), 14 presentaron compromiso subaracnoideo en la convexidad y 13 compromiso subaracnoideo cisternal basal (afectación leptomeníngea). En 13 se observaron tuberculomas y 11 presentaron angeítis de grandes vasos; mientras que 7 tuvieron angeítis de pequeños vasos, 7 hidrocefalia, 6 infartos parenquimatosos y 1 afectación paquimeníngea. Quince pacientes tenían lesiones combinadas. Conclusión. La localización más frecuente de neurotuberculosis en esta serie fue meníngea con compromiso leptomeníngeo (14 pacientes con afectación subaracnoidea, seguido de afectación cisternal en 13 pacientes) y sólo en un caso fue paquimeníngea. La manifestación parenquimatosa más frecuente fue el tuberculoma (granulomas tuberculosos) con 13 casos. De estos, 5 presentaron un patrón miliar y sólo uno comportamiento pseudotumoral.(AU)

Purposes. To report our case series of patients with a diagnosis of intracranial tuberculosis and to describe the different types of lesions characterizing this entity on Magnetic Resonance Imaging (MRI). Materials and Methods. For the present study, we retrospectively selected 20 patients with positive MRI findings of intracranial tuberculosis. Twelve of them were males and 8 were females, with an age range of between 8 months and 49 years (mean age: 21years). Clinical diagnosis was obtained by lumbar puncture and cerebrospinal fluid (CSF) culture. Eleven patients presented positive HIV serology. MRIs were performed using 0.5T and 1.5 T scanners and computed tomography (CT) of the brain was also performed in two patients. Diffusion-weighted technique was performed in two patients and spectroscopy in one patient. Results. Of the total patients studied (n=20), 14 presented convexity subarachnoid involvement and 13 subarachnoid basal cystern involvement (leptomeningeal involvement), 13 presented tuberculomas, 11 large-vessel angiitis, 7 smallvessel angiitis, 7 hydrocephalia, 6 parenchymatous infarction and one pachymeningeal involvement. Combined lesions were observed in 15 patients. Conclusion. The most frequent location of neurotuberculosis in this series was meningeal with leptomeningeal involvement (14 patients with subarachnoid involvement, followed by cysternal involvement in 13 patients), and only one patient had pachymeningeal involvement. The most frequent parenchymatous finding of tuberculosis was tuberculoma in 13 patients, 5 with a miliary pattern and only one with pseudo-tumoral behavior.(AU)

Linfoma Burkitt del seno esfenoidal en pediatría: Reporte de caso / Burkitt Lymphoma of the Sphenoid Sinus in Children: Case Report

Se reporta un caso de linfoma Burkitt del seno esfenoidal en un paciente de sexo masculino, de 3 años de edad, de raza caucásica. Presentaba un cuadro clínico de 10 días de evolución con deterioro del sensorio, vómitos y amaurosis bilateral y, por tomografía computada y resonancia magnética, se identificó una masa que comprometía el seno esfenoidal. Se arribó al diagnóstico por anatomía patológica e inmunomarcación.

We report a case of Burkitt lymphoma of the sphenoid sinus in a 3 year-old caucasian male patient. He presented a clinical condition of 10 days of improvement with a sensory deterioration, vomiting and bilateral amaurosis. A mass which compromised the sphenoid sinus was identified by computed tomography and magnetic resonance imaging. The diagnosis could be reached by pathology and immunohistochemical studies.

Mielitis transversa asociada a vacunación antigripal / Transverse myelitis associated with influenza vaccination

Presentamos el caso de una paciente, de 37 años de edad, con mielitis transversa de comienzo agudo, luego de la aplicación de la vacuna monovalente contra el virus influenza A, subtipo H1N1. El diagnóstico se realizó con resonancia magnética.

We report on a 37-year-old female with acute onset of transverse myelitis after having influenza A (H1N1) monovalent vaccine. The diagnosis was confirmed by magnetic resonance imaging (MRI).

Fibromatosis orbitaria solitaria: reporte de caso

Se reporta un caso de fibromatosis orbitaria solitaria en una paciente de sexo femenino de 4 años de edad, la que acudió a consulta por proptosis derecha y pérdida de la agudeza visual. Por tomografía computada (TC), ecografía y resonancia magnética (RM) se identificó una masa intraconal que comprometía a los músculos extrínsecos de la órbita y hacía impronta sobre el nervio óptico.

Solitary fibrous tumor of the orbit. Case report We report on a 4-year-old female patient with solitary fibrous tumor of the orbit, who presented with right eye ptosis and loss of visual sharpness. Computed tomography (CT) scan, ultrasonography (US) and magnetic resonance imaging (MRI) showed an intraconal mass lesion involving the extrinsic orbit muscles, leaving a depression on the aptic nerve.

Lesiones tendinosas del tobillo en resonancia magnética: análisis retrospectivo en 548 estudios / Tendinous lesions of the ankle in MRI: retrospective review in 548 exams

Objetivo: Determinar la prevalencia de las diversas lesiones tendinosas del tobillo y sus características iconográficas típicas en los pacientes sometidos a Resonancia Magnética (RM). Material y métodos: Se efectuó un análisis descriptivo, retrospectivo y de corte transversal, de 548 estudios de RM de tobillo durante un período de 18 meses (entre enero de 2006 y junio de 2007), que contabiliza el total de los exámenes obtenidos en resonadores de campo cerrado en Diagnóstico por Imágenes Adrogué y en las sedes Hospital Fiorito de Avellaneda y Fundación Científica del Sur. Resultados: Del total de exámenes (n=548), el 40.3% fueron realizados a pacientes de sexo femenino (n=221) y el 59.7% a pacientes de sexo masculino (n=327), con una edad promedio de 47.6 ± 17 años. El 60.5% de los estudios (n=331) no reveló alteraciones en ningún grupo tendinoso del tobillo, mientras que el 39.5% (n=217) demostró la presencia de algún tipo de patología tendinosa. Asimismo, 64 estudios (11.7%) revelaron alteraciones en el tendón tibial posterior; 47 (8.6%) en el tendón de Aquiles; 34 (6.2%) en el tendón peroneo lateral corto; 27 (4.9%) a nivel del tendón del flexor propio del hallux; 26 (4.7%) en el tendón peroneo lateral largo; 10 (1.8%) en el tendón flexor común de los dedos; 6 (1.1%) en el tendón tibial anterior; y 3 (0.5%) en el tendón extensor común de los dedos. Conclusiones: La RM constituye una excelente herramienta en la valoración de las diversas patologías tendinosas debido a su capacidad multiplanar y a su alto contraste tisular.

Purpose: To determine the prevalence of several tendinous lesions of the ankle, and the MR imaging features that characterize these lesions. Materials and methods: MR images in 548 exams of ankle were retrospectively reviewed. These studies were performed during a 18-months period of time in 3 MR scanners at Hospital Fiorito (Avellaneda), Diagnóstico por Imágenes Adrogué, and Fundación Científica del Sur Avellaneda. Results: The ankle MR images (n=548) were taken from 221 women, and 327 men; median age, 47.6 years. In 60.5% studies (n=331), no pathologic images were identified. Sixty four exams (11.7%) showed some kind of tendon injury in the tibialis posterior tendon, 47 (8.6%) in the Achilles tendon, 34 (6.2%) in the peroneus brevis tendon, 27 (4.9%) in the flexor hallucis longus tendon, and 26 (4.7%) in the peroneus longus tendon. Additional findings included lesions in the flexor digitorum longus tendons (n=10), in the tibialis anterior tendon (n=6), and in the extensor digitorum longus tendons (n=3). Conclusions: The high-quality soft-tissue contrast resolution, noninvasive nature, and multiplanar capabilities of the MR images make it an excellent tool for the detection and evaluation of a variety of tendon disorders in the ankle.

Evaluación por TC y RM de tumores orbitarios: nuestra experiencia / Evaluation by TC and RM of orbitarios tumors: our experience

Objetivos: Mostrar nuestra casuística de masas ocupantes de órbita evaluadas por tomografía computada (TC) y/o resonancia magnética (RM). Mencionar los datos imageneológicos y epidemioológicos más relevantes de las mismas obtenidos de la bibliografía, basado en sus diagnósticos diferenciales. Material y métodos: En un período de 48 meses fueron evaluados 26 pacientes con tumores de órbita, 13 de sexo femenino y 13 de sexo masculino, con rango etario entre 3 y 75 años. A 17 pacientes se les realizó RM, a 8, TC, y a uno, ambos métodos. Los equipos utilizados fueron:resonadores de 0.5 y 1,5 Telsa; tomógrafos axial y helicoidal. Resultados: Del total (n=26), 7 fueron tumores benignos, 2 de comportamiento variable y 17 malignos. Los tumores benignos fueron: 2 hemangiomas cavernosos, 1 meningioma, 1 tumor epidermoide, 1 tumor dermoide, 1 lipoma y 1 varice oftálmica. Los tumores de evolución e histología variable fueron: 2 gliomas de nervio óptico. Los tumores malignos examinados resultaron: metástasis, el origen más frecuente, 3 linfomas no Hodgkin, 2 hemangiopericitomas, 2 retinoblastomas, 2 rabdomiosarcomas, 2 melanomas y 1 carcinoma de glándula lagrimal. Dentro de los pacientes con metástasis, el origen más frecuente fue la mama (n=2); otros sitios incluyeron pulmón (n=1), útero (n=1) y neuroblastoma de origen indeterminado (n=1). Conclusión: En nuestra experiencia, 3l 65,4% de los casos correspondio a tumores malignos, siendo más frecuente el secundarismo (19,2%). El 26,9% correspondió a tumores benignos, siendo más frecuente el hemangioma. Un tercer grupo (7.7%) está formado por gliomas de nervio óptico, de histología y comportamiento indeterminados.

Cisticercosis espinal leptomeníngea / Spinal leptomeningeal cysticercosis

La localización espinal de la neurocisticercosis es sumamente rara. Se presenta una paciente de 56 años con antecedentes de hidrocefalia producida por cisticercosis cerebral tratada con válvula de derivación ventriculoperitoneal. Después de dos años consulta por trastornos en la marcha y pérdida de fuerza en miembros inferiores. En el examen neurológico se constata paraparesia espástica, hiperestesia (nivel sensitivo D4-D5) e incontinencia esfinteriana. La RM de columna dorsal evidenció un proceso expansivo quístico intradural extramedular, condicionante de compresión medular. Se practicó una descompensación quirúrgica observándose una aracnoiditis y resecándose un quiste aracnoideo. El análisis anatomopatológico de la pieza reveló una cisticercosis leptomeníngea. La paciente mostró una evolución postquirúrgica favorable con regresión del cuadro neurológico de consulta compresión medular

Cisticercosis espinal leptomeníngea / Spinal leptomeningeal cysticercosis

La localización espinal de la neurocisticercosis es sumamente rara. Se presenta una paciente de 56 años con antecedentes de hidrocefalia producida por cisticercosis cerebral tratada con válvula de derivación ventriculoperitoneal. Después de dos años consulta por trastornos en la marcha y pérdida de fuerza en miembros inferiores. En el examen neurológico se constata paraparesia espástica, hiperestesia (nivel sensitivo D4-D5) e incontinencia esfinteriana. La RM de columna dorsal evidenció un proceso expansivo quístico intradural extramedular, condicionante de compresión medular. Se practicó una descompensación quirúrgica observándose una aracnoiditis y resecándose un quiste aracnoideo. El análisis anatomopatológico de la pieza reveló una cisticercosis leptomeníngea. La paciente mostró una evolución postquirúrgica favorable con regresión del cuadro neurológico de consulta compresión medular (AU)